QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Hussaini, I. M. Articles by VandenBerg, S. R. Search for Related Content PubMed PubMed Citation

Protein kinase C- regulates resistance to UV- and -irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation

Departments of Pathology (Neuropathology) (I.M.H., J.E.C., G.T.R., S.R.V.), Anesthesiology (J.J.S.), and Neurosurgery (M.E.S.), University of Virginia, Charlottesville, VA 22908

² Address correspondence and reprints requests to Isa M. Hussaini, Dept. of Pathology (Neuropathology), The University of Virginia, Charlottesville, VA 22908.

Both increased cell proliferation and apoptosis play important roles in the malignant growth of glioblastomas. We have demonstrated recently that the differential expression of protein kinase C (PKC)- increases the proliferative capacity of glioblastoma cells in culture; however, specific functions for this novel PKC isozyme in the regulation of apoptosis in these tumors has not been defined. In the present study of several glioblastoma cell lines, we investigated the role of PKC- in preventing UV- and -irradiation-induced apoptosis and in caspase-dependent signaling pathways that mediate cell death. Exposure to UV or irradiation killed 80% to 100% of PKC--deficient nonneoplastic human astrocytes and U-1242 MG cells, but had little effect on the PKC--expressing U-251 MG and U-373 MG cells. PKC- appears to mediate resistance to irradiation specifically such that when PKC-h was stably expressed in U-1242 MG cells, more than 80% of these cells developed resistance to irradiation-induced apoptosis. Reducing PKC- expression by transient and stable expression of antisense PKC- in wild-type U-251 MG cells results in increased sensitivity to UV irradiation in a fashion similar to U-1242 MG cells and nonneoplastic astrocytes. Irradiation of PKC--deficient glioblastoma cells resulted in the activation of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and a substantial increase in subdiploid DNA content that did not occur in PKC--expressing tumor cells. A specific inhibitor (Ac-DEVD-CHO) of caspase-3 blocked apoptosis in PKC--deficient U-1242 MG cells. The data demonstrate that resistance to UV and irradiation in glioblastoma cell lines is modified significantly by PKC- expression and that PKC- appears to block the apoptotic cascade at caspase-9 activation.

This article has been cited by other articles:

				Y.-w. Chen, J. E. Cleaver, Z. Hatahet, R. E. Honkanen, J.-Y. Chang, Y. Yen, and K.-m. Chou Human DNA polymerase {eta} activity and translocation is regulated by phosphorylation PNAS, October 28, 2008; 105(43): 16578 - 16583. [Abstract] [Full Text] [PDF]

				M. Entin-Meer, X. Yang, S. R. VandenBerg, K. R. Lamborn, A. Nudelman, A. Rephaeli, and D. A. Haas-Kogan In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas Neuro-oncol, April 1, 2007; 9(2): 82 - 88. [Abstract] [Full Text] [PDF]

				J. Sonnemann, V. Gekeler, A. Sagrauske, C. Muller, H.-P. Hofmann, and J. F. Beck Down-regulation of protein kinase C{eta} potentiates the cytotoxic effects of exogenous tumor necrosis factor-related apoptosis-inducing ligand in PC-3 prostate cancer cells Mol. Cancer Ther., July 1, 2004; 3(7): 773 - 781. [Abstract] [Full Text] [PDF]