|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Tumor Biology |
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030
2 Address correspondence and reprint requests to Ta-Jen Liu, Box 100, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Abstract
Transient expression of the tumor suppressor gene p53 via adenoviral-mediated gene transfer induces apoptosis in glioma cells expressing mutant p53, while causing cell cycle arrest in cells with wild-type p53. To determine whether a change in p53 status of a wild-type p53-expressing cell line such as U-87 MG would alter its apoptotic resistant phenotype in response to Ad-p53 infection, we generated cell lines U-87-175.4 and U-87-175.13 via retroviral-mediated gene transfer of the p53 (175H) mutant into the U-87 MG parental line. Control cell lines U-87-Lux.6 and U-87-Lux.8 were also generated and express the reporter gene luciferase. Both U-87-175.4 and U-87-175.13, but not control cell lines, exhibited morphology characteristic of apoptosis after Ad-p53 infection. Furthermore, expression of other p53 mutants (248W, 273H) in U-87 MG also sensitized cells to Adp53-induced apoptosis. Apoptosis was confirmed by TUNEL and cell cycle analysis. Several p53 response genes were examined in cells infected with Ad-p53, and among these, BCL2, p21WAF1/CIP1, CPP32/caspase 3, and PARP showed differences in expression between U87-175 and U87-Lux cell lines. Taken together, our data demonstrate that the introduction of p53 mutants in U-87 MG promotes an apoptotic response in association with adenoviral-mediated wild-type p53 gene transfer. These results underscore the importance of glioma p53 genotype for predicting tumor response to p53-based gene therapy.
References
An, W.G., Chuman, Y., Fojo, T., and Blagosklonny, M.V. (1998) Inhibitors of transcription, proteasome inhibitors, and DNA feedback of p53 degradation. Exp. Cell Res. 244, 54-60.[CrossRef][Web of Science][Medline]
Carmeliet, P., Dor, Y., Herbert, J.M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., Koch, C.J., Ratcliffe, P., Moons, L., Jain, R.K., Collen, D., and Keshet, E. (1998) Role of HIF-1 in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394,485 -490.[CrossRef][Medline]
Chen, J., Wu, X., Lin, J., and Levine, A.J. (1996) mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol. Cell. Biol. 16,2445 -2452.[Abstract]
Cheng, Y.T., Li, Y.L., Wu, J.D., Long, S.B., Tzai, T.S., Tzeng, C.C., and Lai, M.D. (1995) Overexpression of MDM-2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines. Mol. Carcinog. 13,173 -181.[Web of Science][Medline]
Dameron, K.M., Volpert, O.V., Tainsky, M.A., and Bouck, N.
(1994) Control of angiogenesis in fibroblasts by p53 regulation
of thrombospondin-1. Science
265,1582
-1584.
el-Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B., Parsons, R., Trent, J.M., Lin, D., Mercer, W.E., Kinzler, K.W., and Vogelstein, B. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75,817 -825.[CrossRef][Web of Science][Medline]
el-Deiry, W.S., Harper, J.W., O'Connor, P.M., Velculescu, V.E.,
Canman, C.E., Jackman, J., Pietenpol, J.A., Burrell, M., Hill, D.E., and Wang,
Y. (1994) WAF1/CIP1 is induced in p53-mediated G1 arrest and
apoptosis. Cancer Res.
54,1169
-1174.
Friedlander, P., Haupt, Y., Prives, C., and Oren, M. (1996) A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis. Mol. Cell. Biol. 16,4961 -4971.[Abstract]
Fujiwara, T., Kagawa, S., Ogawa, N., Yasuda, T., Tanaka, N., Orita, K., Cai, D.W., Zhang, W.W., and Roth, J.A. (1996) Recombinant virus-mediated transfer of the wild-type p53 gene is a potent therapeutic strategy for human cancer. Hum. Cell. 9, 25-30.[Medline]
Fults, D., Brockmeyer, D., Tullous, M.W., Pedone, C.A., and
Cawthon, R.M. (1992) p53 mutation and loss of heterozygosity on
chromosomes 17 and 10 during human astrocytoma progression. Cancer
Res. 52,674
-679.
Gomez-Manzano, C., Fueyo, J., Kyritsis, A.P., Steck, P.A., Roth,
J.A., McDonnell, T.J., Steck, K.D., Levin, V.A., and Yung, W.K.
(1996) Adenovirus-mediated transfer of the p53 gene produces
rapid and generalized death of human glioma cells via apoptosis.
Cancer Res. 56,694
-699.
Gomez-Manzano, C., Fueyo, J., Kyritsis, A.P., McDonnell, T.J.,
Steck, P.A., Levin, V.A., and Yung, W.K. (1997) Characterization
of p53 and p21 functional interactions in glioma cells en route to apoptosis.
J. Natl. Cancer Inst.
89,1036
-1044.
Hachiya, M., Chumakov, A., Miller, C.W., Akashi, M., Said, J., and Koeffler, H.P. (1994) Mutant p53 proteins behave in a dominant, negative fashion in vivo. Anticancer Res 14,1853 -1859.[Web of Science][Medline]
He, J., Reifenberger, G., Liu, L., Collins, V.P., and James, C.D. (1994) Analysis of glioma cell lines for amplification and overexpression of MDM2. Genes Chromosomes Cancer 11, 91-96.[Web of Science][Medline]
Hollander, M.C., Alamo, I., Jackman, J., Wang, M.G., McBride, O.W.,
and Fornace, A.J., Jr. (1993) Analysis of the mammalian gadd45
gene and its response to DNA damage. J. Biol. Chem.
268,24385
-24393.
Hupp, T.R., Sparks, A., and Lane, D.P. (1995) Small peptides activate the latent sequence-specific DNA binding function of p53. Cell 83,237 -245.[CrossRef][Web of Science][Medline]
Hsiao, M., Low, J., Dorn, E., Ku, D., Pattengale, P., Yeargin, J., and Haas, M. (1994) Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness. Am. J. Pathol. 145,702 -714.[Abstract]
King, D., Pringle, J.H., Hutchinson, M., and Cohen, G.M. (1998) Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells. Leukemia 12,1553 -1560.[CrossRef][Web of Science][Medline]
Liu, T.J., el-Naggar, A.K., McDonnell, T.J., Steck, K.D., Wang, M.,
Taylor, D.L., and Clayman, G.L. (1995) Apoptosis induction
mediated by wild-type p53 adenoviral gene transfer in squamous cell carcinoma
of the head and neck. Cancer Res.
55,3117
-3122.
Liu, T.J., Wang, M., Breau, R.L., Henderson, Y., El-Naggar, A.K., Steck, K.D., Sicard, M.W., and Clayman, G.L. (1999) Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in growth suppression of head and neck squamous cell carcinoma cell lines. Cancer Gene Ther. 6,163 -171.[CrossRef][Web of Science][Medline]
McDonnell, T.J., Beham, A., Sarkiss, M., Andersen, M.M., and Lo, P. (1996) Importance of the Bcl-2 family in cell death regulation. Experientia 52,1008 -1017.[CrossRef][Web of Science][Medline]
Miyashita, T., and Reed, J.C. (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80,293 -299.[CrossRef][Web of Science][Medline]
Nielsen, L.L., and Maneval, D.C. (1998) P53 tumor suppressor gene therapy for cancer. Cancer Gene Ther. 5, 52-63.[Web of Science][Medline]
Owen-Schaub, L.B., Zhang, W., Cusack, J.C., Angelo, L.S., Santee, S.M., Fujiwara, T., Roth, J.A., Deisseroth, A.B., Zhang, W.W., and Kruzel, E. (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol. Cell. Biol. 15,3032 -3040.[Abstract]
Selivanova, G., Iotsova, V., Okan, I., Fritsche, M., Strom, M., Groner, B., Grafstrom, R.C., and Wiman, K.G. (1997) Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain. Nat. Med. 3, 632-638.[CrossRef][Web of Science][Medline]
Sugrue, M.M., Shin, D.Y., Lee, S.W., and Aaronson, S.A.
(1997) Wild-type p53 triggers a rapid senescence program in human
tumor cells lacking functional p53. Proc. Natl. Acad. Sci.
U.S.A. 94,9648
-9653.
Thornberry, N.A., and Lazebnik, Y. (1998) Caspases:
Enemies within. Science
281,1312
-1316.
Van Meir, E.G., Kikuchi, T., Tada, M., Li, H., Diserens, A.C.,
Wojcik, B.E., Huang, H.J., Friedmann, T., de Tribolet, N., and Cavenee, W.K.
(1994) Analysis of the p53 gene and its expression in human
glioblastoma cells. Cancer Res.
54,649
-652.
Waga, S., Hannon, G.J., Beach, D., and Stillman, B. (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369,574 -578.[CrossRef][Medline]
Yount, G.L., Haas-Kogan, D.A., Vidair, C.A., Haas, M., Dewey, W.C.,
and Israel, M.A. (1996) Cell cycle synchrony unmasks the
influence of p53 function on radiosensitivity of human glioblastoma cells.
Cancer Res. 56,500
-506.
Zhang, W., Shay, J.W., and Deisseroth, A. (1993)
Inactive p53 mutants may enhance the transcriptional activity of wild-type
p53. Cancer Res. 53,4772
-4775.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Nakamizo, T. Amano, W. Zhang, X.-Q. Zhang, L. Ramdas, T.-J. Liu, B. N. Bekele, T. Shono, T. Sasaki, W. F. Benedict, et al. Phosphorylation of Thr18 and Ser20 of p53 in Ad-p53-induced apoptosis Neuro-oncol, January 1, 2008; 10(3): 275 - 291. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
