|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Molecular Genetics |
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany (C.B.K., G.R.); and Neurosurgery/Brain Tumor Research, University Hospitals, Basel, Switzerland (A.M.)
3 Address correspondence and reprint requests to Guido Reifenberger, Department of Neuropathology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Abstract
In 1997, the PTEN gene (phosphatase and tensin homolog deleted on chromosome 10) was identified as a tumor suppressor gene on the long arm of chromosome 10. Since then, important progress has been made with respect to the understanding of the role of the Pten protein in the normal development of the brain as well as in the molecular pathogenesis of human gliomas. This review summarizes the current state of the art concerning the involvement of aberrant Pten function in the development of different biologic features of malignant gliomas, such as loss of cell-cycle control and uncontrolled cell proliferation, escape from apoptosis, brain invasion, and aberrant neoangiogenesis. Most of the tumor-suppressive properties of Pten are dependent on its lipid phosphatase activity, which inhibits the phosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway through dephosphorylation of phosphatidylinositol-(3,4,5)-tri phosphate. The additional function of Pten as a dual-specificity protein phosphatase may also play a role in glioma pathogenesis. Besides the wealth of data elucidating the functional roles of Pten, recent studies suggest a diagnostic significance of PTEN gene alterations as a molecular marker for poor prognosis in anaplastic astrocytomas and anaplastic oligodendrogliomas. Furthermore, the possibility of selective targeting of PTEN mutant tumor cells by specific pharmacologic inhibitors of members of the Pten/PI3K/Akt pathway opens up new perspectives for a targeted molecular therapy of malignant gliomas.
References
Adey, N.B., Huang, L., Ormonde, P.A., Baumgard, M.L., Pero, R.,
Byreddy, D.V., Tavtigian, S.V., and Bartel, P.L. (2000) Threonine
phosphorylation of the MMAC1/Pten PDZ binding domain both inhibits and
stimulates PDZ binding. Cancer Res.
60, 35-37.
Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., and Frame, M.C. (1999) Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18,5646 -5653.[CrossRef][Web of Science][Medline]
Alessi, D.R., Kozlowski, M.T., Weng, Q.P., Morrice, N., and Avruch, J. (1998) 3–Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Curr. Biol. 8,69 -81.[CrossRef][Web of Science][Medline]
Ali, I.U., Schriml, L.M., and Dean, M. (1999)
Mutational spectra of PTEN/MMAC1 gene: A tumor suppressor with lipid
phosphatase activity. J. Natl. Cancer Inst.
91,1922
-1932.
Asada, M., Yamada, T., Ichijo, H., Delia, D., Miyazono, K., Fukumuro, K., and Mizutani, S. (1999) Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. EMBO J. 18,1223 -1234.[CrossRef][Web of Science][Medline]
Backman, S.A., Stambolic, V., Suzuki, A., Haight, J., Elia, A., Pretorius, J., Tsao, M.S., Shannon, P., Bolon, B., Ivy, G.O., and Mak, T.W. (2001) Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat. Genet. 29,396 -403.[CrossRef][Web of Science][Medline]
Blancher, C., Moore, J.W., Robertson, N., and Harris, A.L.
(2001) Effects of ras and von Hippel-Lindau (VHL) gene mutations
on hypoxia-inducible factor (HIF)-1, HIF-2, and vascular endothelial growth
factor expression and their regulation by the phosphatidylinositol
3'-kinase/Akt signaling pathway. Cancer Res.
61,7349
-7355.
Borlado, L.R., Redondo, C., Alvarez, B., Jimenez, C., Criado, L.M.,
Flores, J., Marcos, M.A., Martinez, A.C., Balomenos, D., and Carrera. A.C.
(2000) Increased phosphoinositide 3–kinase activity induces
a lymphoproliferative disorder and contributes to tumor generation in vivo.
FASEB J. 14,895
-903.
Boström, J., Cobbers, J.M.J.L., Wolter, M., Tabatabai, G.,
Weber, R.G., Lichter, P., Collins, V.P., and Reifenberger, G.
(1998) Mutation of the PTEN (MMAC1) tumor suppressor gene in a
subset of glioblastomas but not in meningiomas with loss of chromosome arm
10q. Cancer Res. 58,29
-33.
Burgering, B.M., and Coffer, P.J. (1995) Protein kinase B (c-Akt) in phosphatidylinositol-3–OH kinase signal transduction. Nature 376,599 -602.[CrossRef][Medline]
Chen, H., Rossier, C., Morris, M.A., Scott, H.S., Gos, A., Bairoch, A., and Antonarakis, S.E. (1999) A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y. Hum. Genet. 105,399 -409.[CrossRef][Web of Science][Medline]
Cheney, I.W., Johnson, D.E., Vaillancourt, M.T., Avanzini, J.,
Morimoto, A., Demers, G.W., Wills, K.N., Shabram, P.W., Bolen, J.B.,
Tavtigian, S.V., and Bookstein, R. (1998) Suppression of
tumorigenicity of glioblastoma cells by adenovirus-mediated MMAC1/PTEN gene
transfer. Cancer Res.
58,2331
-2334.
Cheney, I.W., Neuteboom, S.T., Vaillancourt, M.T., Ramachandra, M.,
and Bookstein, R. (1999) Adenovirus-mediated gene transfer of
MMAC1/PTEN to glioblastoma cells inhibits S phase entry by the recruitment of
p27Kip1 into cyclin E/CDK2 complexes. Cancer Res.
59,2318
-2323.
Cheng, J.Q., Godwin, A.K., Bellacosa, A., Taguchi, T., Franke,
T.F., Hamilton, T.C., Tsichlis, P.N., and Testa, J.R. (1992)
AKT2, a putative oncogene encoding a member of a subfamily of
protein-serine/threonine kinases, is amplified in human ovarian carcinomas.
Proc. Natl. Acad. Sci. U.S.A.
89,9267
-9271.
Cheng, J.Q., Ruggeri, B., Klein, W.M., Sonoda, G., Altomare, D.A.,
Watson, D.K., and Testa, J.R. (1996) Amplification of AKT2 in
human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by
antisense RNA. Proc. Natl. Acad. Sci. U.S.A.
93,3636
-3641.
Chiariello, E., Roz, L., Albarosa, R., Magnani, I., and Finocchiaro, G. (1998) PTEN/MMAC1 mutations in primary glioblastomas and short-term cultures of malignant gliomas. Oncogene 16,541 -545.[CrossRef][Web of Science][Medline]
Chiariello, E., Roz, L., Albarosa, R., Magnani, I., and Finocchiaro, G. (1999) Identification of PTEN-related sequences in glioma cells and in nonneoplastic cell lines. Cancer Lett. 138,1 -4.[CrossRef][Web of Science][Medline]
Dahia, P.L., FitzGerald, M.G., Zhang, X., Marsh, D.J., Zheng, Z., Pietsch, T., von Deimling, A., Haluska, F.G., Haber, D.A., and Eng, C. (1998) A highly conserved processed PTEN pseudogene is located on chromosome band 9p21. Oncogene 16,2403 -2406.[CrossRef][Web of Science][Medline]
Davies, M.A., Lu, Y., Sano, T., Fang, X., Tang, P., LaPushin, R.,
Koul, D., Bookstein, R., Stokoe, D., Yung, W.K., Mills, G.B., and Steck, P.A.
(1998) Adenoviral transgene expression of MMAC/PTEN in human
glioma cells inhibits Akt activation and induces anoikis. Cancer
Res. 58,5285
-5290.
Davies, M.P., Gibbs, F.E., Halliwell, N., Joyce, K.A., Roebuck, M.M., Rossi, M.L., Salisbury, J., Sibson, D.R., Tacconi, L., and Walker, C. (1999) Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas. Br. J. Cancer 79,1542 -1548.[CrossRef][Web of Science][Medline]
Di Cristofano, A., and Pandolfi, P.P. (2000) The multiple roles of Pten in tumor suppression. Cell 100,387 -390.[CrossRef][Web of Science][Medline]
Di Cristofano, A., Pesce, B., Cordon-Cardo, C., and Pandolfi, P.P. (1998) Pten is essential for embryonic development and tumor suppression. Nat. Genet. 19,348 -355.[CrossRef][Web of Science][Medline]
Di Cristofano, A., Kotsi, P., Peng, Y.F., Cordon-Cardo, C., Elkon,
K.B., and Pandolfi, P.P. (1999) Impaired Fas response and
autoimmunity in PTEN+/- mice. Science
285,2122
-2125.
Di Cristofano A., De Acetis M., Koff A., Cordon-Cardo C., and Pandolfi, P.P. (2001) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27,222 -224.[CrossRef][Web of Science][Medline]
Duerr, E.M., Rollbrocker, B., Hayashi, Y., Peters, N., Meyer-Puttlitz, B., Louis, D.N., Schramm, J., Wiestler, O.D., Parsons, R., Eng, C., and von Deimling, A. (1998) PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16,2259 -2264.[CrossRef][Web of Science][Medline]
Ebert, C., von Haken, M., Meyer-Puttlitz, B., Wiestler, O.D.,
Reifenberger, G., Pietsch, T., and von Deimling, A. (1999)
Molecular genetic analysis of ependymal tumors: NF2 mutations and chromosome
22q loss occur preferentially in intramedullary spinal ependymomas.
Am. J. Pathol. 155,627
-632.
Forgacs, E., Biesterveld, E.J., Sekido, Y., Fong, K., Muneer, S., Wistuba, I.I., Milchgrub, S., Brezinschek, R., Virmani, A., Gazdar, A.F., and Minna, J.D. (1998) Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene 17,1557 -1565.[CrossRef][Web of Science][Medline]
Franke, T.F., Yang, S.I., Chan, T.O., Datta, K., Kazlauskas, A., Morrison, D.K., Kaplan, D.R., and Tsichlis, P.N. (1995) The protein kinase encoded by the AKT proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3–kinase. Cell 81,727 -736.[CrossRef][Web of Science][Medline]
Fujii, G.H., Morimoto, A.M., Berson, A.E., and Bolen, J.B. (1999) Transcriptional analysis of the PTEN/MMAC1 pseudogene, psiPTEN. Oncogene 18,1765 -1769.[CrossRef][Web of Science][Medline]
Fults, D., and Pedone, C. (2000) Immunocytochemical mapping of the phosphatase and tensin homolog (Pten/MMAC1) tumor suppressor protein in human gliomas. Neuro-Oncology [serial online], Doc. 99–28, March 22, 2000. URL <neuro-oncology.mc.duke.edu>. Neuro-Oncology 2,71 -79.[Abstract]
Furnari, F.B., Lin, H., Huang, H.S., and Cavenee, W.K.
(1997) Growth suppression of glioma cells by Pten requires a
functional phosphatase catalytic domain. Proc. Natl. Acad. Sci.
U.S.A. 94,12479
-12484.
Furnari, F.B., Huang, H.J.S., and Cavenee, W.K. (1998)
The phosphoinositol phosphatase activity of Pten mediates a serum-sensitive
G1 growth arrest in glioma cells. Cancer
Res. 58,5002
-5008.
Fuse, T., Tanikawa, M., Nakanishi, M., Ikeda, K., Tada, T., Inagaki, H., Asai, K., Kato, T., and Yamada, K. (2000) p27Kip1 expression by contact inhibition as a prognostic index of human glioma. J. Neurochem. 74,1393 -1399.[CrossRef][Web of Science][Medline]
Geoerger, B., Kerr, K., Tang, C.B., Fung, K.M., Powell, B., Sutton,
L.N., Phillips, P.C., and Janss, A.J. (2001) Antitumor activity
of the rapamycin analog CCI-779 in human primitive neuroectodermal
tumor/medulloblastoma models as single agent and in combination chemotherapy.
Cancer Res. 61,1527
-1532.
Georgescu, M.M., Kirsch, K.H., Akagi, T., Shishido, T., and
Hanafusa, H. (1999) The tumor-suppressor activity of PTEN is
regulated by its carboxyl-terminal region. Proc. Natl. Acad. Sci.
U.S.A. 96,10182
-10187.
Georgescu, M.M., Kirsch, K.H., Kaloudis, P., Yang, H., Pavletich,
N.P., and Hanafusa, H. (2000) Stabilization and productive
positioning roles of the C2 domain of Pten tumor suppressor. Cancer
Res. 60,7033
-7038.
Gescher, A. (1998) Analogs of staurosporine: Potential anticancer drugs? Gen. Pharmacol. 31,721 -728.[Web of Science][Medline]
Gimm, O., Attie-Bitach, T., Lees, J.A., Vekemans, M., and Eng, C.
(2000a) Expression of the Pten tumor suppressor protein during
human development. Hum. Mol. Genet.
9,1633
-1639.
Gimm, O., Perren, A., Weng, L.P., Marsh, D.J., Yeh, J.J., Ziebold,
U., Gil, E., Hinze, R., Delbridge, L., Lees, J.A., Mutter, G.L., Robinson,
B.G., Komminoth, P., Dralle, H., and Eng, C. (2000b) Differential
nuclear and cytoplasmic expression of Pten in normal thyroid tissue, and
benign and malignant epithelial thyroid tumors. Am. J.
Pathol. 156,1693
-1700.
Giri, D., and Ittmann, M. (1999) Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma. Hum. Pathol. 30,419 -424.[CrossRef][Web of Science][Medline]
Gottschalk, A.R., Basila, D., Wong, M., Dean, N.M., Brandts, C.H.,
Stokoe, D., and Haas-Kogan, D.A. (2001) p27Kip1 is
required for Pten-induced G1 growth arrest. Cancer
Res. 61,2105
-2111.
Groszer, M., Erickson, R., Scripture-Adams, D., Lesche, R., Trumpp,
A., Zack, J.A., Kornblum, H.I., Liu, X., and Wu, H. (2001)
Negative regulation of neural stem/progenitor cell proliferation by the PTEN
tumor suppressor gene in vivo. Science
294,2186
-2189.
Gu, J., Tamura, M., and Yamada, K.M. (1998) Tumor
suppressor Pten inhibits integrin- and growth factor-mediated
mitogen-activated protein (MAP) kinase signaling pathways. J. Cell
Biol. 143,1375
-1383.
Gu, J., Tamura, M., Pankov, R., Danen, E.H., Takino, T., Matsumoto,
K., and Yamada, K.M. (1999) Shc and FAK differentially regulate
cell motility and directionality modulated by Pten. J. Cell
Biol. 146,389
-403.
Guipponi, M., Tapparel, C., Jousson, O., Scamuffa, N., Mas, C., Rossier, C., Hutter, P., Meda, P., Lyle, R., Reymond, A., and Antonarakis, S.E. (2001) The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family. Hum. Genet. 109,569 -575.[CrossRef][Web of Science][Medline]
Haas-Kogan, D., Shalev, N., Wong, M., Mills, G., Yount, G., and Stokoe, D. (1998) Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr. Biol. 8,1195 -1198.[CrossRef][Web of Science][Medline]
He, J., Mokhtari, K., Sanson, M., Marie, Y., Kujas, M., Huguet, S., Leuraud, P., Capelle, L., Delattre, J.Y., Poirier, J., and Hoang-Xuan, K. (2001) Glioblastomas with an oligodendroglial component: A pathological and molecular study. J. Neuropathol. Exp. Neurol. 60,863 -871.[Web of Science][Medline]
Hidalgo, M., and Rowinsky, E.K. (2000) The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene 19,6680 -6686.[CrossRef][Web of Science][Medline]
Hill, M.M., Andjelkovic, M., Brazil, D.P., Ferrari, S., Fabbro, D.,
and Hemmings, B.A. (2001) Insulin-stimulated protein kinase B
phosphorylation on Ser-473 is independent of its activity and occurs through a
staurosporine-insensitive kinase. J. Biol. Chem.
276,25643
-25646.
Holland, E.C., Celestino, J., Dai, C., Schaefer, L., Sawaya, R.E., and Fuller, G.N. (2000) Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat. Genet. 25,55 -57.[CrossRef][Web of Science][Medline]
Hui, A.B., Lo, K.W., Yin, X.L., Poon, W.S., and Ng, H.K. (2001) Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab. Invest. 81,717 -723.[Web of Science][Medline]
Jiang, B.H., Jiang, G., Zheng, J.Z., Lu, Z., Hunter, T., and Vogt,
P.K. (2001) Phosphatidylinositol 3–kinase signaling
controls levels of hypoxia-inducible factor 1. Cell Growth
Differ. 12,363
-369.
Jones, G., Machado, J., Jr., Tolnay, M., and Merlo, A.
(2001a) Pten-independent induction of caspase-mediated cell death
and reduced invasion by the focal adhesion targeting domain (FAT) in human
astrocytic brain tumors which highly express focal adhesion kinase (FAK).
Cancer Res. 61,5688
-5691.
Jones, G., Machado, J., Jr., and Merlo, A. (2001b)
Loss of focal adhesion kinase (FAK) inhibits epidermal growth factor
receptor-dependent migration and induces aggregation of nh(2)-terminal FAK in
the nuclei of apoptotic glioblastoma cells. Cancer
Res. 61,4978
-4981.
Kato, H., Kato, S., Kumabe, T., Sonoda, Y., Yoshimoto, T., Kato,
S., Han, S.Y., Suzuki, T., Shibata, H., Kanamaru, R., and Ishioka, C.
(2000) Functional evaluation of p53 and PTEN gene mutations in
gliomas. Clin. Cancer Res.
6,3937
-3943.
Knobbe, C.B., and Reifenberger, G. (2001) Molecular genetic analysis of human glioblastomas for aberrations of genes encoding members of the Pten/PI3K/Akt signal transduction pathway. Neuro-Oncology [serial online], Doc. A153, September 24, 2001. URL <neuro-oncology.mc.duke.edu>. Neuro-Oncology 3,304 . (Abstract)
Kotelevets, L., van Hengel, J., Bruyneel, E., Mareel, M., van Roy,
F., and Chastre, E. (2001) The lipid phosphatase activity of Pten
is critical for stabilizing intercellular junctions and reverting
invasiveness. J. Cell Biol.
155,1129
-1135.
Koul, D., Parthasarathy, R., Shen, R., Davies, M.A., Jasser, S.A., Chintala, S.K., Rao, J.S., Sun, Y., Benvenisite, E.N., Liu, T.J., and Yung, W.K. (2001) Suppression of matrix metalloproteinase-2 gene expression and invasion in human glioma cells by MMAC/PTEN. Oncogene 20,6669 -6678.[CrossRef][Web of Science][Medline]
Kraus, J.A., Lamszus, K., Glesmann, N., Beck, M., Wolter, M., Sabel, M., Krex, D., Klockgether, T., Reifenberger, G., and Schlegel, U. (2001) Molecular genetic alterations in glioblastomas with oligodendroglial component. Acta Neuropathol. 101,311 -320.[Medline]
Kubiatowski, T., Jang, T., Lachyankar, M.B., Salmonsen, R., Nabi, R.R., Quesenberry, P.J., Litofsky, N.S., Ross, A.H., and Recht, L.D. (2001) Association of increased phosphatidylinositol 3–kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J. Neurosurg. 95,480 -488.[Web of Science][Medline]
Kubota, N., Okada, S., Inada, T., Ohnishi, K., and Ohnishi, T. (2000) Wortmannin sensitizes human glioblastoma cell lines carrying mutant and wild type TP53 gene to radiation. Cancer Lett. 161,141 -147.[CrossRef][Web of Science][Medline]
Kwon, C.H., Zhu, X., Zhang, J., Knoop, L.L., Tharp, R., Smeyne, R.J., Eberhart, C.G., Burger, P.C., and Baker, S.J. (2001) Pten regulates neuronal soma size: A mouse model of Lhermitte-Duclos disease. Nat. Genet. 29,404 -411.[CrossRef][Web of Science][Medline]
Lachyankar, M.B., Sultana, N., Schonhoff, C.M., Mitra, P., Poluha,
W., Lambert, S., Quesenberry, P.J., Litofsky, N.S., Recht, L.D., Nabi, R.,
Miller, S.J., Ohta, S., Neel, B.G., and Ross, A.H. (2000) A role
for nuclear Pten in neuronal differentiation. J.
Neurosci. 20,1404
-1413.
Lee, J.O., Yang, H., Georgescu, M.M., Di Cristofano, A., Maehama, T., Shi, Y., Dixon, J.E., Pandolfi, P., and Pavletich, N.P. (1999) Crystal structure of the Pten tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association. Cell 99,323 -334.[CrossRef][Web of Science][Medline]
Li, D.M., and Sun, H. (1997) TEP1, encoded by
a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase
regulated by transforming growth factor beta. Cancer
Res. 57,2124
-2129.
Li, D.M., and Sun, H. (1998) Pten/MMAC1/Tep1
suppresses the tumorigenicity and induces G1 cell cycle arrest in human
glioblastoma cells. Proc. Natl. Acad. Sci. U.S.A.
95,15406
-15411.
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S.I.,
Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S.H., Giovanella,
B.C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M.H., and Parsons, R.
(1997) PTEN, a putative tyrosine phosphatase gene mutated in
human brain, breast, and prostate cancer. Science
275,1943
-1947.
Li, J., Simpson, L., Takahashi, M., Miliaresis, C., Myers, M.P.,
Tonks, N., and Parsons, R. (1998) The Pten/MMAC1 tumor suppressor
induces cell death that is rescued by the AKT/protein kinase B
oncogene. Cancer Res.
58,5667
-5672.
Liaw, D., Marsh, D.J., Li, J., Dahia, P.L., Wang, S.I., Zheng, Z., Bose, S., Call, K.M., Tsou, H.C., Peacocke, M., Eng, C., and Parsons, R. (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 16,64 -67.[CrossRef][Web of Science][Medline]
Liliental, J., Moon, S.Y., Lesche, R., Mamillapalli, R., Li, D., Zheng, Y., Sun, H., and Wu, H. (2000) Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr. Biol. 10,401 -404.[CrossRef][Web of Science][Medline]
Lin, H., Bondy, M.L., Langford, L.A., Hess, K.R., Delclos, G.L.,
Wu, X., Chan, W., Pershouse, M.A., Yung, W.K., and Steck, P.A.
(1998) Allelic deletion analyses of MMAC/PTEN and DMBT1 loci in
gliomas: Relationship to prognostic significance. Clin. Cancer
Res. 4,2447
-2454.
Liu, W., James, C.D., Frederick, L., Alderete, B.E., and Jenkins,
R.B. (1997) PTEN/MMAC1 mutations and EGFR amplification in
glioblastomas. Cancer Res.
57,5254
-5257.
Ma, Y.Y., Wei, S.J., Lin, Y.C., Lung, J.C., Chang, T.C., Whang-Peng, J., Liu, J.M., Yang, D.M., Yang, W.K., and Shen, C.Y. (2000) PIK3CA as an oncogene in cervical cancer. Oncogene 19,2739 -2744.[CrossRef][Web of Science][Medline]
Maehama, T., and Dixon, J.E. (1998) The tumor
suppressor, Pten/Mmac1, dephosphorylates the lipid second messenger,
phosphatidylinositol 3,4,5–trisphosphate. J. Biol.
Chem. 273,13375
-13378.
Maehama, T., Taylor, G.S., and Dixon, J.E. (2001) Pten and myotubularin: Novel phosphoinositide phophatases. Annu. Rev. Biochem. 70,247 -279.[CrossRef][Web of Science][Medline]
Maier, D., Zhang, Z., Taylor, E., Hamou, M.F., Gratzl, O., Van Meir, E.G., Scott, R.J., and Merlo, A. (1998) Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25–26 region as the primary target in low-grade and high-grade gliomas. Oncogene 16,3331 -3335.[CrossRef][Web of Science][Medline]
Maier, D., Jones, G., Li, X., Schonthal, A.H., Gratzl, O., Van
Meir, E.G., and Merlo, A. (1999) The Pten lipid phosphatase
domain is not required to inhibit invasion of glioma cells. Cancer
Res. 59,5479
-5482.
Maity, A., Pore, N., Lee, J., Solomon, D., and O'Rourke, D.M.
(2000) Epidermal growth factor receptor transcriptionally
up-regulates vascular endothelial growth factor expression in human
glioblastoma cells via a pathway involving phosphatidylinositol
3'-kinase and distinct from that induced by hypoxia. Cancer
Res. 60,5879
-5886.
Maity, A., Pore, N., Haas-Kogan, D.A., and O'Rourke, D.M. (2001) PTEN mutation cooperates with EGFR activation in human glioblastoma cells to increase VEGF mRNA levels by transactivating an element in the proximal promoter. Int. J. Radiat. Oncol. Biol. Phys. 51 (Suppl. 1),101 -102.
Malmer, B., Gronberg, H., Andersson, U., Jonsson, B.A., and Henriksson, R. (2001) Microsatellite instability, PTEN and p53 germline mutations in glioma families. Acta Oncol. 40,633 -637.[CrossRef][Web of Science][Medline]
Mamillapalli, R., Gavrilova, N., Mihaylova, V.T., Tsvetkov, L.M., Wu, H., Zhang, H., and Sun, H. (2001) Pten regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2). Curr. Biol. 11,263 -267.[CrossRef][Web of Science][Medline]
Marsh, D.J., Dahia, P.L., Zheng, Z., Liaw, D., Parsons, R., Gorlin, R.J., and Eng, C. (1997) Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat. Genet. 16,333 -334.[CrossRef][Web of Science][Medline]
Marsh, D.J., Kum, J.B., Lunetta, K.L., Bennett, M.J., Gorlin, R.J.,
Ahmed, S.F., Bodurtha, J., Crowe, C., Curtis, M.A., Dasouki, M., Dunn, T.,
Feit, H., Geraghty, M.T., Graham, J.M, Jr., Hodgson, S.V., Hunter, A., Korf,
B.R., Manchester, D., Miesfeldt, S., Murday, V.A., Nathanson, K.L., Parisi,
M., Pober, B., Romano, C., Eng, C., et al. (1999) PTEN mutation
spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba
syndrome suggest a single entity with Cowden syndrome. Hum. Mol.
Genet. 8,1461
-1472.
Mayo, L.D., Dixon, J.E., Durden, D.L., Tonks, N.K., and Donner,
D.B. (2002) Pten protects p53 from Mdm2 and sensitizes cancer
cells to chemotherapy. J. Biol. Chem.
277,5484
-5489.
Medema, R.H., Kops, G.J., Bos, J.L., and Burgering, B.M. (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404,782 -787.[CrossRef][Medline]
Mills, G.B., Lu, Y.L., and Kohn, E.C. (2001) Linking
molecular therapeutics to molecular diagnostics: Inhibition of the
FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant
cells in vitro and in vivo. Proc. Natl. Acad. Sci.
U.S.A. 98,10031
-10033.
Nakamura, N., Ramaswamy, S., Vazquez, F., Signoretti, S., Loda, M.,
and Sellers, W.R. (2000) Forkhead transcription factors are
critical effectors of cell death and cell cycle arrest downstream of Pten.
Mol. Cell. Biol. 20,8969
-8982.
Nave, B.T., Ouwens, M., Withers, D.J., Alessi, D.R., and Shepherd, P.R. (1999) Mammaliantarget of rapamycin is a direct target for protein kinase B: Identification of a convergence point for opposing effects of insulin and aminoacid deficiency on protein translation. Biochem. J. 344,427 -431.
Neshat, M.S., Mellinghoff, I.K., Tran, C., Stiles, B., Thomas, G.,
Petersen, R., Frost, P., Gibbons, J.J., Wu, H., and Sawyers, C.L.
(2001) Enhanced sensitivity of PTEN-deficient tumors to
inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. U.S.A.
98,10314
-10319.
Ng, S.S., Tsao, M.S., Nicklee, T., and Hedley, D.W.
(2001) Wortmannin inhibits PKB/Akt phosphorylation and promotes
gemcitabine antitumor activity in orthotopic human pancreatic cancer
xenografts in immunodeficient mice. Clin. Cancer Res.
7,3269
-3275.
Olschwang, S., Serova-Sinilnikova, O.M., Lenoir, G.M., and Thomas, G. (1998) PTEN germ-line mutations in juvenile polyposis coli. Nat. Genet. 18,12 -14.[CrossRef][Web of Science][Medline]
Paramio, J.M., Navarro, M., Segrelles, C., Gomez-Casero, E., and Jorcano, J.L. (1999) Pten tumor suppressor is linked to the cell cycle control through the retinoblastoma protein. Oncogene 18,7462 -7468.[CrossRef][Web of Science][Medline]
Peraud, A., Watanabe, K., Schwechheimer, K., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1999) Genetic profile of the giant cell glioblastoma. Lab. Invest. 79,123 -129.[Web of Science][Medline]
Persad, S., Troussard, A.A., McPhee, T.R., Mulholland, D.J., and
Dedhar, S. (2001) Tumor suppressor Pten inhibits nuclear
accumulation of betacatenin and T cell/lymphoid enhancer factor
1–mediated transcriptional activation. J. Cell
Biol. 153,1161
-1174.
Piva, R., Cavalla, P., Bortolotto, S., Cordera, S., Richiardi, P., and Schiffer, D. (1997) p27/kip1 expression in human astrocytic gliomas. Neurosci. Lett. 234,127 -130.[CrossRef][Web of Science][Medline]
Podsypanina, K., Ellenson, L.H., Nemes, A., Gu, J., Tamura, M.,
Yamada, K.M., Cordon-Cardo, C., Catoretti, G., Fisher, P.E., and Parsons, R.
(1999) Mutation of PTEN/MMAC1 in mice causes neoplasia in
multiple organ systems. Proc. Natl. Acad. Sci. U.S.A.
96,1563
-1568.
Podsypanina,K., Lee, R.T., Politis, C., Hennessy, I., Crane, A.,
Puc, J., Neshat, M., Wang, H., Yang, L., Gibbons, J., Frost, P., Dreisbach,
V., Blenis, J., Gaciong, Z., Fisher, P., Sawyers, C., Hedrick-Ellenson, L.,
and Parsons, R. (2001) An inhibitor of mTOR reduces neoplasia and
normalizes p70/S6 kinase activity in PTEN+/- mice. Proc.
Natl. Acad. Sci. U.S.A. 98,10320
-10325.
Powis, G., Bonjouklian, R., Berggren, M.M., Gallegos, A., Abraham,
R., Ashendel, C., Zalkow, L., Matter, W.F., Dodge, J., and Grindey, G.
(1994) Wortmannin, a potent and selective inhibitor of
phosphatidylinositol-3–kinase. Cancer Res.
54,2419
-2423.
Radimerski, T., Montagne, J., Rintelen, F., Stocker, H., van der Kaay, J., Downes, C.P., Hafen, E., and Thomas, G. (2002) dS6K regulated cell growth is dPKB/dPI3K independent, but requires dPDK1. Nat. Cell Biol. 4,251 -255.[CrossRef][Web of Science][Medline]
Raffel, C., Frederick, L., O'Fallon, J.R., Atherton-Skaff, P.,
Perry, A., Jenkins, R.B., and James, C.D. (1999) Analysis of
oncogene and tumor suppressor gene alterations in pediatric malignant
astrocytomas reveals reduced survival for patients with PTEN mutations.
Clin. Cancer Res. 5,4085
-4090.
Rasheed, B.K., Stenzel, T.T., McLendon, R.E., Parsons, R.,
Friedman, A.H., Friedman, H.S., Bigner, D.D., and Bigner, S.H.
(1997) PTEN gene mutations are seen in high-grade but not in
low-grade gliomas. Cancer Res.
57,4187
-4190.
Reis, R.M., Konu-Lebleblicioglu, D., Lopes, J.M., Kleihues, P., and
Ohgaki, H. (2000) Genetic profile of gliosarcomas. Am.
J. Pathol. 156,425
-432.
Salvesen, H.B., MacDonald, N., Ryan, A., Jacobs, I.J., Lynch, E.D., Akslen, L.A., and Das, S. (2001) PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int. J. Cancer 91,22 -26.[CrossRef][Web of Science][Medline]
Sano, T., Lin, H., Chen, X., Langford, L.A., Koul, D., Bondy, M.L.,
Hess, K.R., Myers, J.N., Hong, Y.K., Yung, W.K., and Steck, P.A.
(1999) Differential expression of MMAC/Pten in glioblastoma
multiforme: Relationship to localization and prognosis. Cancer
Res. 59,1820
-1824.
Sasaki, H., Zlatescu, M.C., Betensky, R.A., Ino, Y., Cairncross,
J.G., and Louis, D.N. (2001) PTEN is a target of chromosome 10q
loss in anaplastic oligodendrogliomas and PTEN alterations are associated with
poor prognosis. Am. J. Pathol.
159,359
-367.
Scheid, M.P., and Woodgett, J.R. (2001) PKB/AKT: Functional insights from genetic models. Nat. Rev. Mol. Cell Biol. 2,760 -768.[CrossRef][Web of Science][Medline]
Schmelzle, T., and Hall, M.N. (2000) TOR, a central controller of cell growth. Cell 103,253 -262.[CrossRef][Web of Science][Medline]
Schmidt, E.E., Ichimura, K., Goike, H.M., Moshref, A., Liu, L., and Collins, V.P. (1999) Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts. J. Neuropathol. Exp. Neurol. 58,1170 -1183.[Web of Science][Medline]
Sekulic, A., Hudson, C.C., Homme, J.L., Yin, P., Otterness, D.M.,
Karnitz, L.M., and Abraham, R.T. (2000) A direct linkage between
the phosphoinositide 3–kinase-AKT signaling pathway and the mammalian
target of rapamycin in mitogen-stimulated and transformed cells.
Cancer Res. 60,3504
-3513.
Sharrard, R.M., and Maitland, N.J. (2000) Alternative splicing of the human PTEN/MMAC1/TEP1 gene. Biochim. Biophys. Acta 1494,282 -285.[Medline]
Shayesteh, L., Lu, Y., Kuo, W.L., Baldocchi, R., Godfrey, T., Collins, C., Pinkel, D., Powell, B., Mills, G.B., and Gray, J.W. (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet. 21,99 -102.[CrossRef][Web of Science][Medline]
Simpson, L., and Parsons, R. (2001) Pten: Life as a tumor suppressor. Exp. Cell Res. 264, 29-41.[CrossRef][Web of Science][Medline]
Smith, J.S., Tachibana, I., Passe, S.M., Huntley, B.K., Borell,
T.J., Iturria, N., O'Fallon, J.R., Schaefer, P.L., Scheithauer, B.W., James,
C.D., Buckner, J.C., and Jenkins, R.B. (2001) PTEN mutation, EGFR
amplification, and outcome in patients with anaplastic astrocytoma and
glioblastoma multiforme. J. Natl. Cancer Inst.
93,1246
-1256.
Sonoda, Y., Ozawa, T., Aldape, K.D., Deen, D.F., Berger, M.S., and
Pieper, R.O. (2001) Akt pathway activation converts anaplastic
astrocytoma to glioblastoma multiforme in a human astrocyte model of glioma.
Cancer Res. 61,6674
-6678.
Stambolic, V., Suzuki, A., de la Pompa, J.L., Brothers, G.M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J.M., Siderovski, D.P., and Mak, T.W. (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor Pten. Cell 95, 29-39.[CrossRef][Web of Science][Medline]
Stambolic, V., MacPherson, D., Sas, D., Lin, Y., Snow, B., Jang, Y., Benchimol, S., and Mak, T.W. (2001) Regulation of PTEN transcription by p53. Mol. Cell 8, 317-325.[CrossRef][Web of Science][Medline]
Steck, P.A., Pershouse, M.A., Jasser, S.A., Yung, W.K., Lin, H., Ligon, A.H., Langford, L.A., Baumgard, M.L., Hattier, T., Davis, T., Frye, C., Hu, R., Swedlund, B., Teng, D.H., and Tavtigian, S.V. (1997) Identification of a candidate tumor suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15,356 -362.[CrossRef][Web of Science][Medline]
Stein, R.C. (2001) Prospects for phosphoinositide 3–kinase inhibition as a cancer treatment. Endocr. Relat. Cancer 8,237 -248.[Abstract]
Suzuki, A., de la Pompa, J.L., Stambolic, V., Elia, A.J., Sasaki, T., del Barco Barrantes, I., Ho, A., Wakeham, A., Itie, A., Khoo, W., Fukumoto, M., and Mak, T.W. (1998) High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr. Biol. 8,1169 -1178.[CrossRef][Web of Science][Medline]
Suzuki, A., Yamaguchi, M.T., Ohteki, T., Sasaki, T., Kaisho, T., Kimura, Y., Yoshida, R., Wakeham, A., Higuchi, T., Fukumoto, M., Tsubata, T., Ohashi, P.S., Koyasu, S., Penninger, J.M., Nakano, T., and Mak, T.W. (2001) T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14,523 -534.[CrossRef][Web of Science][Medline]
Tachibana, I., Smith, J.S., Sato, K., Hosek, S.M., Kimmel, D.W., and Jenkins, R.B. (2000) Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. Am. J. Med. Genet. 92,136 -141.[CrossRef][Web of Science][Medline]
Tada, K., Shiraishi, S., Kamiryo, T., Nakamura, H., Hirano, H., Kuratsu, J., Kochi, M., Saya, H., and Ushio, Y. (2001) Analysis of loss of heterozygosity on chromosome 10 in patients with malignant astrocytic tumors: Correlation with patient age and survival. J. Neurosurg. 95,651 -659.[Web of Science][Medline]
Tamura, M., Gu, J., Matsumoto, K., Aota, S., Parsons, R., and
Yamada, K.M. (1998) Inhibition of cell migration, spreading, and
focal adhesions by tumor suppressor Pten. Science
280,1614
-1617.
Tamura, M., Gu, J., Takino, T., and Yamada, K.M.
(1999) Tumor suppressor PTEN inhibition of cell invasion,
migration, and growth: Differential involvement of focal adhesion kinase and
p130Cas. Cancer Res. 59,442
-449.
Tian, X.X., Pang, J.C., To, S.S., and Ng, H.K. (1999) Restoration of wild-type Pten expression leads to apoptosis, induces differentiation, and reduces telomerase activity in human glioma cells. J. Neuropathol. Exp. Neurol. 58,472 -479.[Web of Science][Medline]
Tohma, Y., Gratas, C., Biernat, W., Peraud, A., Fukuda, M., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1998) PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J. Neuropathol. Exp. Neurol. 57,684 -689.[Web of Science][Medline]
Tolkacheva, T., and Chan, A.M. (2000) Inhibition of H-Ras transformation by the PTEN/MMAC1/TEP1 tumor suppressor gene. Oncogene 19,680 -689.[CrossRef][Web of Science][Medline]
Torres, J., and Pulido R. (2001) The tumor suppressor
Pten is phosphorylated by the protein kinase CK2 at its C terminus:
Implications for Pten stability to proteasome-mediated degradation.
J. Biol. Chem. 276,993
-998.
Tortosa, A., Ino, Y., Odell, N., Swilley, S., Sasaki, H., Louis, D.N., and Henson, J.W. (2000) Molecular genetics of radiographically defined de novo glioblastoma multiforme. Neuropathol. Appl. Neurobiol. 26,544 -552.[CrossRef][Web of Science][Medline]
Vanhaesebroeck, B., and Alessi, D.R. (2000) The PI3K-PDK1 connection: More than just a road to PKB. Biochem. J. 346,561 -576.
Vazquez, F., Grossman, S.R., Takahashi, Y., Rokas, M.V., Nakamura,
N., and Sellers, W.R. (2001) Phosphorylation of the Pten tail
acts as an inhibitory switch by preventing its recruitment into a protein
complex. J. Biol. Chem.
276,48627
-48630.
Virolle, T., Adamson, E.D., Baron, V., Birle, D., Mercola, D., Mustelin, T., and de Belle, I. (2001) The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling. Nat. Cell Biol. 3,1124 -1128.[CrossRef][Web of Science][Medline]
Vlahos, C.J., Matter, W.F., Hui, K.Y., and Brown, R.F.
(1994) A specific inhibitor of phosphatidylinositol
3–kinase,
2–(4–morpholinyl)-8–phenyl-4H-1–benzopyran-4–one
(LY294002). J. Biol. Chem.
269,5241
-5248.
Walker, C., Joyce, K.A., Thompson-Hehir, J., Davies, M.P., Gibbs, F.E., Halliwell, N., Lloyd, B.H., Machell, Y., Roebuck, M.M., Salisbury, J., Sibson, D.R., Du Plessis, D., Broome, J., and Rossi, M.L. (2001) Characterisation of molecular alterations in microdissected archival gliomas. Acta Neuropathol. 101,321 -333.[Medline]
Walker, S.M., Downes, C.P., and Leslie, N.R. (2001) TPIP: A novel phosphoinositide 3–phosphatase. Biochem. J. 360,277 -283.[CrossRef][Web of Science][Medline]
Wang, D., Huang, H.J., Kazlauskas, A., and Cavenee, W.K.
(1999) Induction of vascular endothelial growth factor expression
in endothelial cells by platelet-derived growth factor through the activation
of phosphatidylinositol 3–kinase. Cancer Res.
59,1464
-1472.
Wang, S.I., Puc, J., Li, J., Bruce, J.N., Cairns, P., Sidransky,
D., and Parsons, R. (1997) Somatic mutations of PTEN in
glioblastoma multiforme. Cancer Res.
57,4183
-4186.
Watanabe, K., Peraud, A., Gratas, C., Wakai, S., Kleihues, P., and Ohgaki, H. (1998) p53 and PTEN gene mutations in gemistocytic astrocytomas. Acta Neuropathol. 95,559 -564.[CrossRef][Medline]
Wen, S., Stolarov, J., Myers, M.P., Su, J.D., Wigler, M.H., Tonks,
N.K., and Durden, D.L. (2001) Pten controls tumor-induced
angiogenesis. Proc. Natl. Acad. Sci. U.S.A.
98,4622
-4627.
Weng, L.P., Smith, W.M., Brown, J.L., and Eng, C.
(2001a) Pten inhibits insulin-stimulated MEK/MAPK activation and
cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex
formation in a breast cancer model. Hum. Mol. Genet.
10,605
-616.
Weng, L.P., Brown, J.L., and Eng, C. (2001b) Pten
coordinates G(1) arrest by down-regulating cyclin D1 via its protein
phosphatase activity and up-regulating p27 via its lipid phosphatase activity
in a breast cancer model. Hum. Mol. Genet.
10,599
-604.
Whang, Y.E., Wu, X., Suzuki, H., Reiter, R.E., Tran, C., Vessella,
R.L., Said, J.W., Isaacs, W.B., and Sawyers, C.L. (1998)
Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate
cancer through loss of expression. Proc. Natl. Acad. Sci.
U.S.A. 95,5246
-5250.
Wick, W., Furnari, F.B., Naumann, U., Cavenee, W.K., and Weller, M. (1999) PTEN gene transfer in human malignant glioma: Sensitization to irradiation and CD95L-induced apoptosis. Oncogene 18,3936 -3943.[CrossRef][Web of Science][Medline]
Wiestler, O.D., Padberg, G.W., and Steck, P.A. (2000) Cowden disease and dysplastic gangliocytoma of the cerebellum/Lhermitte-Duclos disease. In: Kleihues, P., and Cavenee, W.K. (Eds.), Pathology and Genetics of Tumours of the Nervous System. WHO Classification of Tumors. Lyon, France: IARC Press. pp.235 -237.
Wu, R.C., Li, X., and Schonthal, A.H. (2000) Transcriptional activation of p21WAF1 by Pten/MMAC1 tumor suppressor. Mol. Cell. Biochem. 203, 59-71.[CrossRef][Web of Science][Medline]
Wu, X., Senechal, K., Neshat, M.S., Whang, Y.E., and Sawyers, C.L.
(1998) The Pten/MMAC1 tumor suppressor phosphatase functions as a
negative regulator of the phosphoinositide 3–kinase/Akt pathway.
Proc. Natl. Acad. Sci. U.S.A.
95,15587
-15591.
Wu, X., Hepner, K., Castelino-Prabhu, S., Do, D., Kaye, M.B., Yuan,
X.J., Wood, J., Ross, C., Sawyers, C.L., and Whang, Y.E. (2000)
Evidence for regulation of the Pten tumor suppressor by a membrane-localized
multi-PDZ domain containing scaffold protein MAGI-2. Proc. Natl.
Acad. Sci. U.S.A. 97,4233
-4238.
Wu, Y., Dowbenko, D., Spencer, S., Laura, R., Lee, J., Gu, Q., and
Lasky, L.A. (2000) Interaction of the tumor suppressor Pten/MMAC
with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase.
J. Biol. Chem. 275,21477
-21485.
Wu, Y., Dowbenko, D., Pisabarro, M.T., Dillard-Telm, L., Koeppen,
H., and Lasky, L.A. (2001) Pten 2, a
Golgi-associatedtestis-specific homologue of the Pten tumor suppressor lipid
phosphatase. J. Biol. Chem.
276,21745
-21753.
Yamada, K.M., and Araki, M. (2001) Tumor suppressor
Pten: Modulator of cell signaling, growth, migration and apoptosis.
J. Cell Sci. 114,2375
-2382.
Yart, A., Laffargue, M., Mayeux, P., Chretien, S., Peres, C.,
Tonks, N., Roche, S., Payrastre, B., Chap, H., and Raynal, P.
(2001) A critical role for phosphoinositide 3–kinase
upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated
protein kinases by epidermal growth factor. J. Biol.
Chem. 276,8856
-8864.
Zhang, C.L., Tada, M., Kobayashi, H., Nozaki, M., Moriuchi, T., and Abe, H. (2000) Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay. Oncogene 19,4346 -4353.[CrossRef][Web of Science][Medline]
Zhang, W., Yamada, H., Sakai, N., and Nozawa, Y. (1993) Sensitization of C6 glioma cells to radiation by staurosporine, a potent protein kinase C inhibitor. J. Neurooncol. 15,1 -7.[CrossRef][Medline]
Zhou, B.P., Liao, Y., Xia, W., Zou, Y., Spohn, B., and Hung, M.C. (2001a) HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat. Cell Biol. 3, 973-982.[CrossRef][Web of Science][Medline]
Zhou, B.P., Liao, Y., Xia, W., Spohn, B., Lee, M.H., and Hung, M.C. (2001b) Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol. 3,245 -252.[CrossRef][Web of Science][Medline]
Zhou, X.P., Li, Y.J., Hoang-Xuan, K., Laurent-Puig, P., Mokhtari, K., Longy, M., Sanson, M., Delattre, J.Y., Thomas, G., and Hamelin, R. (1999a) Mutational analysis of the PTEN gene in gliomas: Molecular and pathological correlations. Int. J. Cancer 84,150 -154.[CrossRef][Web of Science][Medline]
Zhou, X.P., Sanson, M., Hoang-Xuan, K., Robin, E., Taillandier, L., He, J., Mokhtari, K., Cornu, P., Delattre, J.Y., Thomas, G., and Hamelin,R. (1999b) Germline mutations of p53 but not p16/CDKN2 or PTEN/MMAC1 tumor suppressor genes predispose to gliomas. The ANOCEF Group. Association des NeuroOncologues d'Expression Francaise. Ann. Neurol. 46,913 -916.[CrossRef][Web of Science][Medline]
Zhou, X.-P., Hampel, H., Thiele, H., Gorlin, R.J., Hennekam, R.C.M., Parisi, M., Winter, R.M., and Eng, C. (2001) Association of germline mutation in the PTEN tumor suppressor gene and Proteus and Proteus-like syndromes. Lancet 358,210 -211.[CrossRef][Web of Science][Medline]
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F.,
Chen, E., Gottschalk, A.R., Ryan, H.E., Johnson, R.S., Jefferson, A.B.,
Stokoe, D., and Giaccia, A.J. (2000) Loss of Pten facilitates
HIF-1–mediated gene expression. Genes Dev.
14,391
-396.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Griffero, A. Daga, D. Marubbi, M. C. Capra, A. Melotti, A. Pattarozzi, M. Gatti, A. Bajetto, C. Porcile, F. Barbieri, et al. Different Response of Human Glioma Tumor-initiating Cells to Epidermal Growth Factor Receptor Kinase Inhibitors J. Biol. Chem., March 13, 2009; 284(11): 7138 - 7148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Giussani, L. Brioschi, R. Bassi, L. Riboni, and P. Viani Phosphatidylinositol 3-Kinase/AKT Pathway Regulates the Endoplasmic Reticulum to Golgi Traffic of Ceramide in Glioma Cells: A LINK BETWEEN LIPID SIGNALING PATHWAYS INVOLVED IN THE CONTROL OF CELL SURVIVAL J. Biol. Chem., February 20, 2009; 284(8): 5088 - 5096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, F. Guessous, S. Kwon, M. Kumar, O. Ibidapo, L. Fuller, E. Johnson, B. Lal, I. Hussaini, Y. Bao, et al. PTEN Has Tumor-Promoting Properties in the Setting of Gain-of-Function p53 Mutations Cancer Res., March 15, 2008; 68(6): 1723 - 1731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Kuhn, S. M. Chang, P. Y. Wen, T. F. Cloughesy, H. Greenberg, D. Schiff, C. Conrad, K. L. Fink, H. I. Robins, M. Mehta, et al. Pharmacokinetic and Tumor Distribution Characteristics of Temsirolimus in Patients with Recurrent Malignant Glioma Clin. Cancer Res., December 15, 2007; 13(24): 7401 - 7406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohgaki and P. Kleihues Genetic Pathways to Primary and Secondary Glioblastoma Am. J. Pathol., May 1, 2007; 170(5): 1445 - 1453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Radeff-Huang, T. M. Seasholtz, J. W. Chang, J. M. Smith, C. T. Walsh, and J. H. Brown Tumor Necrosis Factor-{alpha}-stimulated Cell Proliferation Is Mediated through Sphingosine Kinase-dependent Akt Activation and Cyclin D Expression J. Biol. Chem., January 12, 2007; 282(2): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Schaffer, H. Kamino, A. Witkiewicz, J. M. McNiff, and S. J. Orlow Mucocutaneous Neuromas: An Underrecognized Manifestation of PTEN Hamartoma-Tumor Syndrome. Arch Dermatol, May 1, 2006; 142(5): 625 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Edwards, M. Verreault, B. Thiessen, W. H. Dragowska, Y. Hu, J. H.F. Yeung, S. Dedhar, and M. B. Bally Combined inhibition of the phosphatidylinositol 3-kinase/Akt and Ras/mitogen-activated protein kinase pathways results in synergistic effects in glioblastoma cells. Mol. Cancer Ther., March 1, 2006; 5(3): 645 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pore, S. Liu, H.-K. Shu, B. Li, D. Haas-Kogan, D. Stokoe, J. Milanini-Mongiat, G. Pages, D. M. O'Rourke, E. Bernhard, et al. Sp1 Is Involved in Akt-mediated Induction of VEGF Expression through an HIF-1-independent Mechanism Mol. Biol. Cell, November 1, 2004; 15(11): 4841 - 4853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ohgaki, P. Dessen, B. Jourde, S. Horstmann, T. Nishikawa, P.-L. Di Patre, C. Burkhard, D. Schuler, N. M. Probst-Hensch, P. C. Maiorka, et al. Genetic Pathways to Glioblastoma: A Population-Based Study Cancer Res., October 1, 2004; 64(19): 6892 - 6899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-A. O. Nathan, N. Amirghahari, F. Abreo, X. Rong, G. Caldito, M. L. Jones, H. Zhou, M. Smith, D. Kimberly, and J. Glass Overexpressed eIF4E Is Functionally Active in Surgical Margins of Head and Neck Cancer Patients via Activation of the Akt/Mammalian Target of Rapamycin Pathway Clin. Cancer Res., September 1, 2004; 10(17): 5820 - 5827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Knobbe, J. Reifenberger, B. Blaschke, and G. Reifenberger Hypermethylation and Transcriptional Downregulation of the Carboxyl-Terminal Modulator Protein Gene in Glioblastomas J Natl Cancer Inst, March 17, 2004; 96(6): 483 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Musatov, J. Roberts, A. I. Brooks, J. Pena, S. Betchen, D. W. Pfaff, and M. G. Kaplitt Inhibition of neuronal phenotype by PTEN in PC12 cells PNAS, March 9, 2004; 101(10): 3627 - 3631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van den Boom, M. Wolter, R. Kuick, D. E. Misek, A. S. Youkilis, D. S. Wechsler, C. Sommer, G. Reifenberger, and S. M. Hanash Characterization of Gene Expression Profiles Associated with Glioma Progression Using Oligonucleotide-Based Microarray Analysis and Real-Time Reverse Transcription-Polymerase Chain Reaction Am. J. Pathol., September 1, 2003; 163(3): 1033 - 1043. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
