This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Google Scholar Google Scholar Articles by Mandil, R. Articles by Brodie, C. Search for Related Content PubMed PubMed Citation Articles by Mandil, R. Articles by Brodie, C.

Protein Kinase C and Protein Kinase C Play Opposite Roles in the Proliferation and Apoptosis of Glioma Cells¹

Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel 52900 [R. M., M. B., I. K., G. K., C. B.]; Department of Neurosurgery, Hadassa Medical Center, Jerusalem, Israel [E. A., G. R., F. U.]; and Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892 [P. S. L., P. M. B.]

Protein kinase C (PKC) has been implicated in the proliferation and apoptosis of glial tumors, but the role of specific PKC isoforms remains unresolved. Comparing brain tumors differing in degree of malignancy, we found that malignant gliomas expressed higher levels of PKC and lower levels of PKC as compared with low-grade astrocytomas. Consistent with a mechanistic role for these differences, overexpression of PKC in the human U87 glioma cell line resulted in enhanced cell proliferation and decreased glial fibrillary acidic protein (GFAP) expression as compared with controls. Reciprocally, overexpression of PKC inhibited cell proliferation and enhanced GFAP expression. Using PKC chimeras, we found that the regulatory domains of PKC and PKC mediated their effects on cell proliferation and GFAP expression. PKC and have been implicated as potential signaling molecules in apoptosis. Therefore, we examined the role of these isoforms in the resistance of glioma cells to apoptotic stimuli. In U87 cells, manipulation of PKC levels had little effect on apoptosis in response to etoposide. In contrast, overexpression of PKC rendered the U87 cells more sensitive to the apoptotic effect of etoposide, and PKC was cleaved in these cells by a caspase-dependent process. Furthermore, the glioma cell line U373, which expresses endogenous PKC, underwent apoptosis in response to etoposide, and the apoptotic response was blocked by the PKC inhibitor rottlerin. Our results suggest that PKC and PKC play opposite roles in the proliferation and apoptosis of glioma cells.

This article has been cited by other articles:

				A. Magnifico, L. Albano, S. Campaner, M. Campiglio, S. Pilotti, S. Menard, and E. Tagliabue Protein Kinase C{alpha} Determines HER2 Fate in Breast Carcinoma Cells with HER2 Protein Overexpression without Gene Amplification Cancer Res., June 1, 2007; 67(11): 5308 - 5317. [Abstract] [Full Text] [PDF]

				Y.-H. Hsieh, T.-T. Wu, C.-Y. Huang, Y.-S. Hsieh, J.-M. Hwang, and J.-Y. Liu p38 Mitogen-Activated Protein Kinase Pathway Is Involved in Protein Kinase C{alpha}-Regulated Invasion in Human Hepatocellular Carcinoma Cells Cancer Res., May 1, 2007; 67(9): 4320 - 4327. [Abstract] [Full Text] [PDF]

				J. M Haughian, T. A Jackson, D. M Koterwas, and A. P Bradford Endometrial cancer cell survival and apoptosis is regulated by protein kinase C {alpha} and {delta} Endocr. Relat. Cancer, December 1, 2006; 13(4): 1251 - 1267. [Abstract] [Full Text] [PDF]

				V. Aaltonen, J. Koivunen, M. Laato, and J. Peltonen Heterogeneity of Cellular Proliferation within Transitional Cell Carcinoma: Correlation of Protein Kinase C Alpha/betaI Expression and Activity J. Histochem. Cytochem., July 1, 2006; 54(7): 795 - 806. [Abstract] [Full Text] [PDF]

				M. Nakagawa, J. L. Oliva, D. Kothapalli, A. Fournier, R. K. Assoian, and M. G. Kazanietz Phorbol Ester-induced G1 Phase Arrest Selectively Mediated by Protein Kinase C{delta}-dependent Induction of p21 J. Biol. Chem., October 7, 2005; 280(40): 33926 - 33934. [Abstract] [Full Text] [PDF]

				H. Okhrimenko, W. Lu, C. Xiang, N. Hamburger, G. Kazimirsky, and C. Brodie Protein Kinase C-{varepsilon} Regulates the Apoptosis and Survival of Glioma Cells Cancer Res., August 15, 2005; 65(16): 7301 - 7309. [Abstract] [Full Text] [PDF]

				T. Hara, Y. Saito, T. Hirai, K. Nakamura, K. Nakao, M. Katsuki, and K. Chida Deficiency of Protein Kinase C{alpha} in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis Cancer Res., August 15, 2005; 65(16): 7356 - 7362. [Abstract] [Full Text] [PDF]

				S. Gillespie, X. D. Zhang, and P. Hersey Variable expression of protein kinase C{varepsilon} in human melanoma cells regulates sensitivity to TRAIL-induced apoptosis Mol. Cancer Ther., April 1, 2005; 4(4): 668 - 676. [Abstract] [Full Text] [PDF]

				H.-W. Lo, G. R. Antoun, and F. Ali-Osman The Human Glutathione S-Transferase P1 Protein Is Phosphorylated and Its Metabolic Function Enhanced by the Ser/Thr Protein Kinases, cAMP-Dependent Protein Kinase and Protein Kinase C, in Glioblastoma Cells Cancer Res., December 15, 2004; 64(24): 9131 - 9138. [Abstract] [Full Text] [PDF]

				E. Deutsch, A. Cohen, G. Kazimirsky, S. Dovrat, H. Rubinfeld, C. Brodie, and R. Sarid Role of Protein Kinase C {delta} in Reactivation of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., September 15, 2004; 78(18): 10187 - 10192. [Abstract] [Full Text] [PDF]

				J. Koivunen, V. Aaltonen, S. Koskela, P. Lehenkari, M. Laato, and J. Peltonen Protein Kinase C {alpha}/{beta} Inhibitor Go6976 Promotes Formation of Cell Junctions and Inhibits Invasion of Urinary Bladder Carcinoma Cells Cancer Res., August 15, 2004; 64(16): 5693 - 5701. [Abstract] [Full Text] [PDF]

				X.-H. Jiang, S.-P. Tu, J.-T. Cui, M. C. M. Lin, H. H. X. Xia, W. M. Wong, A. O.-O. Chan, M. F. Yuen, S.-H. Jiang, S.-K. Lam, et al. Antisense Targeting Protein Kinase C {alpha} and {beta}1 Inhibits Gastric Carcinogenesis Cancer Res., August 15, 2004; 64(16): 5787 - 5794. [Abstract] [Full Text] [PDF]

				J. Liu, J. Chen, Q. Dai, and R. M. Lee Phospholipid Scramblase 3 Is the Mitochondrial Target of Protein Kinase C {delta}-induced Apoptosis Cancer Res., March 15, 2003; 63(6): 1153 - 1156. [Abstract] [Full Text] [PDF]

				A. S. Clark, K. A. West, P. M. Blumberg, and P. A. Dennis Altered Protein Kinase C (PKC) Isoforms in Non-Small Cell Lung Cancer Cells: PKC{delta} Promotes Cellular Survival and Chemotherapeutic Resistance Cancer Res., February 15, 2003; 63(4): 780 - 786. [Abstract] [Full Text] [PDF]

				B. K. Berdiev, J. Xia, B. Jovov, J. M. Markert, T. B. Mapstone, G. Y. Gillespie, C. M. Fuller, J. K. Bubien, and D. J. Benos Protein Kinase C Isoform Antagonism Controls BNaC2 (ASIC1) Function J. Biol. Chem., November 22, 2002; 277(48): 45734 - 45740. [Abstract] [Full Text] [PDF]

				B. C. Morrish and M. G. Rumsby The 5' Untranslated Region of Protein Kinase C{delta} Directs Translation by an Internal Ribosome Entry Segment That Is Most Active in Densely Growing Cells and during Apoptosis Mol. Cell. Biol., September 1, 2002; 22(17): 6089 - 6099. [Abstract] [Full Text] [PDF]

				K. M. Lounsbury, M. Stern, D. Taatjes, S. Jaken, and B. T. Mossman Increased Localization and Substrate Activation of Protein Kinase C{delta} in Lung Epithelial Cells following Exposure to Asbestos Am. J. Pathol., June 1, 2002; 160(6): 1991 - 2000. [Abstract] [Full Text] [PDF]

				R. T. M. Boudreau, R. Garduno, and T.-J. Lin Protein Phosphatase 2A and Protein Kinase Calpha Are Physically Associated and Are Involved in Pseudomonas aeruginosa-induced Interleukin 6 Production by Mast Cells J. Biol. Chem., February 8, 2002; 277(7): 5322 - 5329. [Abstract] [Full Text] [PDF]

				A. B. da Rocha, D.R.A. Mans, A. Regner, and G. Schwartsmann Targeting Protein Kinase C: New Therapeutic Opportunities Against High-Grade Malignant Gliomas? Oncologist, February 1, 2002; 7(1): 17 - 33. [Abstract] [Full Text] [PDF]

				M. Blass, I. Kronfeld, G. Kazimirsky, P. M. Blumberg, and C. Brodie Tyrosine Phosphorylation of Protein Kinase C{delta} Is Essential for Its Apoptotic Effect in Response to Etoposide Mol. Cell. Biol., January 1, 2002; 22(1): 182 - 195. [Abstract] [Full Text] [PDF]