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Review

PKCη as a therapeutic target in glioblastoma multiforme

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Pages 299-313 | Published online: 22 Apr 2005

Bibliography

  • HOLLAND EC: Gliomagenesis: genetic alterations and mouse models. Nat. Rev Genet. (2001) 2(2):120–129.
  • •A concise review that describes the genetic changes associated with primary brain tumours.
  • MISCHEL PS, NELSON SF, CLOUGHESY TF: Molecular analysis of glioblastoma: pathway profiling and its implications for patient therapy. Cancer Biol. Ther. (2003) 2(3):242–247.
  • MAHER EA, FURNARI FB, BACHOO RM et al: Malignant glioma: genetics and biology of a grave matter. Genes Dev. (2001) 15(11):1311–1333.
  • MISCHEL PS, CLOUGHESY TF: Targeted molecular therapy of GBM. Brain Pathol (2003) 13(1):52–61.
  • COULD WELL WT, UHM JH, ANTEL JP, YONG VW: Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. Neurosurgery (1991) 29(6):880–887.
  • BENZIL DL, FINKELSTEIN SD, EPSTEIN MH, FINCH PW: Expression pattern of alpha-protein kinase C in human astrocytomas indicates a role in malignant progression. Cancer Res. (1992) 52(10):2951–2956.
  • COULD WELL WT, ANTEL JP, YONG VW: Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C. Neurosurgery (1992) 31(4):717–724; discussion 724.
  • BESSON A, YONG VW: Mitogenic Signaling and the relationship to cell cycle regulation in astrocytomas. Neuro-Oncology (2001) 51(4):245–264.
  • BREDEL M, POLLACK IF: The role of protein kinase C (PKC) in the evolution and proliferation of malignant gliomas, and the application of PKC inhibition as a novel approach to anti-glioma therapy. Acta Neurochir. (Wien) (1997) 139(11):1000–1013.
  • HUSSAINI IM, KARNS LR, VINTON G et al: Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells. J. Biol. Chem. (2000) 275(29):22348–22354.
  • ••This work demonstrates the growthadvantage conferred by PKCti expression in human glioblastoma cell lines.
  • HUSSAINI IM, CARPENTER JE, REDPATH GT et al: Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation. Neuro-oncol (2002) 4(1):9–21.
  • ••This work describes the role of PKCII inpreventing apoptosis after radiation in human glioblastoma cell lines.
  • NISHIZUKA Y: The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature (1988) 334(6184):661–665.
  • •This paper represents a seminal paper in the study of PKCs.
  • PARKER PJ, MURRAY-RUST J: PKC at a glance. Cell Sci. (2004) 117(Pt 2):131–132.
  • ••This recent review highlights theregulation of PKC activation and PKC interacting proteins.
  • HURLEY JH, NEWTON AC, PARKER PJ, BLUMBERG PM, NISHIZUKA Y: Taxonomy and function of Cl protein kinase C homology domains. Protein Sci. (1997) 6(2):477–480.
  • KAZANIETZ MG, BUSTELO XR, BARBACID M: Zinc finger domains and phorbol ester pharmacophore. Analysis of binding to mutated form of protein kinase C zeta and the vav and c-raf proto-oncogene products. J. Biol Chem. (1994) 269(15):11590–11594.
  • PEARS CJ, KOUR G, HOUSE C, KEMP BE, PARKER PJ: Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation. Eur. Biochem. (1990) 194(1):89–94.
  • NISHIZUKA Y: The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature (1984) 308(5961):693–698.
  • GOTO K, KONDO H: Diacylglycerol kinase in the central nervous system-molecular heterogeneity and gene expression. Chem. Phys. Lipids (1999) 98(1-2):109–117.
  • NEWTON AC: Regulation of protein kinase C. Curr. Opin. Cell Biol. (1997) 9(2):161–167.
  • NEWTON AC: Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem. Rev (2001) 101(8):2353–2364.
  • NEWTON AC: Protein kinase C: structure, function, and regulation. J. Biol. Chem. (1995) 270(48):28495–28498.
  • TREMBLAY F, LAVIGNE C, JACQUES H, MARETTE A: Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/ protein kinase B and atypical protein kinase C (zeta/lambda) activities. Diabetes (2001) 50(8):1901–1910.
  • CHOU MM, HOU W, JOHNSON J et al: Regulation of protein kinase C zeta by PI 3-kinase and PDK-1. Curr. Biol. (1998) 8(19):1069–1077.
  • AEDER SE, MARTIN PM, SOH JW, HUSSAINI IM: PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene (2004) 23(56):9062–9069.
  • KRONER C, EYBRECHTS K, AKKERMAN JW: Dual regulation of platelet protein kinase B. J. Biol. Chem. (2000) 275(36):27790–27798.
  • KAWAKAMI Y, NISHIMOTO H, KITAURA J et al.: Protein kinase C beta II regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion. J. Biol. Chem. (2004)
  • SCHONWASSER DC, MARAIS RM, MARSHALL CJ, PARKER PJ: Activation of the mitogen-activated protein kinase/ extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Mol Cell. Biol. (1998) 18(2):790–798.
  • ••A comprehensive study investigating theregulation of MAPK signaling downstream of PKC activation.
  • MARAIS R, LIGHT Y, MASON C et al: Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C. Science (1998) 280(5360):109–112.
  • BRANDLIN I, HUBNER S, EISELER T et al: Protein kinase C (PKC)eta-mediated PKC mu activation modulates ERK and JNK signal pathways. I Biol. Chem. (2002) 277(8):6490–6496.
  • BESSON A, YONG VW: Involvement of p21(Wafl/Cip1) in protein kinase C alpha-induced cell cycle progression. Mol Cell. Biol. (2000) 20(13):4580–4590.
  • CASTAGNA M, TAKAI Y, KAIBUCHI K et al: Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J. Biol. Chem. (1982) 257(13):7847–7851.
  • DA ROCHA AB, MANS DR, REGNER A, SCHWARTSMANN G: Targeting protein kinase C: new therapeutic opportunities against high-grade malignant gliomas? Oncologist (2002) 7(1):17–33.
  • •A comprehensive review of PKCs as molecular targets in GBM.
  • MACKAY HJ, TWELVES CJ: Protein kinase C: a target for anticancer drugs? Endocr. Relat. Cancer (2003) 10(3):389–396.
  • •A review article discussing the use of PKC inhibitors as treatments for cancer.
  • DETJEN KM, BREMBECK FH, WELZEL M et al.: Activation of protein kinase Calpha inhibits growth of pancreatic cancer cells via p21(cip)-mediated G(1) arrest. J. Cell Sci. (2000) 113 (Pt 17):3025–3035.
  • DENHAM DW, FRANZ MG, DENHAM W et al.: Directed antisense therapy confirms the role of protein kinase C-alpha in the tumorigenicity of pancreatic cancer. Surgery (1998) 124(2):218–223; discussion 223–214.
  • BASU A, WEIXEL K, SAIJO N: Characterization of the protein kinase C signal transduction pathway in cisplatin-sensitive and -resistant human small cell lung carcinoma cells. Cell Growth Differ. (1996) 7(10:1507–1512.
  • WANG XY, REPASKY E, LIU HT: Antisense inhibition of protein kinase Calpha reverses the transformed phenotype in human lung carcinoma cells. Exp. Cell Res. (1999) 250(1):253–263.
  • MAWRIN C, DIETE S, TREUHEIT T et al.: Prognostic relevance of MAPK expression in glioblastoma multiforme. Int. J. Oncol (2003) 23(3):641–648.
  • MURRAY NR, DAVIDSON LA, CHAPKIN RS et al: Overexpression of protein kinase C betaII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. J. Cell Biol. (1999) 145(4):699–711.
  • ZHANG J, ANASTASIADIS PZ, LIU Y, THOMPSON EA, FIELDS AP: Protein kinase C (PKC) betall induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway. J. Biol. Chem. (2004) 279(21):22118–22123.
  • PERSONS DA, OWEN RD, OSTROWSKI MC, FINN OJ: Protein kinase C gamma expression mimics phorbol ester-induced transcriptional activation of a murine VL30 enhancer element. Cell Growth Differ. (1991) 2(1):7–14.
  • PERSONS DA, WILKISON WO, BELL RM, FINN OJ: Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA. Cell (1988) 52(3):447–458.
  • MAZZONI E, ADAM A, BAL DE KIER JOFFE E, AGUIRRE-GHISO JA: Immortalized mammary epithelial cells overexpressing protein kinase C gamma acquire a malignant phenotype and become tumorigenic in vivo. Mol Cancer Res. (2003) 1(10):776–787.
  • NI H, ERGIN M, TIBUDAN SS et al: Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis. BE J. Haematol (2003) 121(6):849–856.
  • MCCRACKEN MA, MIRAGLIA LJ, MCKAY RA, STROBL JS: Protein kinase C delta is a prosurvival factor in human breast tumor cell lines. Mol. Cancer Ther. (2003) 2(3):273–281.
  • JANSEN AP, VERWIEBE EG, DRECKSCHMIDT NE et al: Protein kinase C-epsilon transgenic mice: a unique model for metastatic squamous cell carcinoma. Cancer Res. (2001) 61(3):808–812.
  • KILEY SC, CLARK KJ, DUDDY SK, WELCH DR, JAKEN S: Increased protein kinase C delta in mammary tumor cells: relationship to transformtion and metastatic progression. Oncogene (1999) 18(48):6748–6757.
  • DING L, WANG H, LANG W, XIAO L: Protein kinase C-epsilon promotes survival of lung cancer cells by suppressing apoptosis through dysregulation of the mitochondrial caspase pathway. J. Biol. Chem. (2002) 277(38):35305–35313.
  • MCJILTON MA, VAN SIKES C, WESCOTT GG et al: Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells. Oncogene (2003) 22(39):7958–7968.
  • BECK J, HAND GRETINGER R, KLINGEBIEL T et al: Expression of PKC isozyme and MDR-associated genes in primary and relapsed state AML. Leukemia (1996) 10(3):426–433.
  • WAYS DK, POSEKANY K, DEVENTE J et al.: Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation. Cell Growth Differ. (1994) 5(10:1195–1203.
  • SHIH SC, MULLEN A, ABRAMS K, MUKHOPADHYAY D, CLAFFEY KP: Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells. .1 Biol. Chem. (1999) 274(22):15407–15414.
  • XIAO H, GOLDTHWAIT DA, MAPSTONE T: The identification of four protein kinase C isoforms in human glioblastoma cell lines: PKC alpha, gamma, epsilon, and zeta. J. Neurosurg. (1994) 81(5):734–740.
  • LAUDANNA C, SORIO C, TECCHIO C et al.: Motility analysis of pancreatic adenocarcinoma cells reveals a role for the atypical zeta isoform of protein kinase C in cancer cell movement. Lab. Invest. (2003) 83(8):1155–1163.
  • WEICHERT W, GEKELER V, DENKERT C, DIETEL M, HAUPTMANN S: Protein kinase C isoform expression in ovarian carcinoma correlates with indicators of poor prognosis. Int. J. Oncol (2003) 23(3):633–639.
  • MURRAY NR, FIELDS AP: Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis. ./. Biol. Chem. (1997) 272(44):27521–27524.
  • MURRAY NR, JAMIESON L, YU W et al.: Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J. Cell Biol. (2004) 164(6):797–802.
  • BRUGGER D, BRISCHWEIN K, LIU C et al.: Induction of drug resistance and protein kinase C genes in A2780 ovarian cancer cells after incubation with antineoplastic agents at sublethal concentrations. Anti-Cancer Res. (2002) 22(6C):4229–4232.
  • BECK J, BOHNET B, BRUGGER D et al: Multiple gene expression analysis reveals distinct differences between G2 and G3 stage breast cancers, and correlations of PKC eta with MDR1, MRP and LRP gene expression. BE J. Cancer (1998) 77(1):87–91.
  • LANGZAM L, KOREN R, GAL R et a/.: Patterns of protein kinase C isoenzyme expression in transitional cell carcinoma of bladder. Relation to degree of malignancy. Am. J. Clin. Pathol (2001) 116(3):377–385.
  • BRENNER W, FARBER G, HERGET T et al: Protein kinase C eta is associated with progression of renal cell carcinoma (RCC). Anti-Cancer Res. (2003) 23(5A):4001–4006.
  • MASSO-WELCH PA, WINSTON JS, EDGES et al: Altered expression and localization of PKC eta in human breast tumors. Breast Cancer Res. Treat. (2001) 68(3):211–223.
  • AKKARAJU GR, BASU A: Overexpression of protein kinase C-eta attenuates caspase activation and tumor necrosis factor-alpha-induced cell death. Biochem. Biophys. Res. Commun. (2000) 279(1):103–107.
  • MATSUMURA M, TANAKA N, KUROKI T, ICHIHASHI M, OHBA M: The eta isoform of protein kinase C inhibits UV-induced activation of caspase-3 in normal human keratinocytes. Biochem. Biophys. Res. Commun. (2003) 303(1):350–356.
  • •PKCII as an antiapoptotic regulatory protein in human skin cells.
  • OHBA M, ISHINO K, KASHIWAGI M et al.: Induction of differentiation in normal human keratinocytes by adenovirus-mediated introduction of the eta and delta isoforms of protein kinase C. Mol Cell. Biol. (1998) 18(9):5199–5207.
  • CHIDA K, HARA T, HIRAI T et al: Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis. Cancer Res. (2003) 63(10):2404–2408.
  • MISRA-PRESS A, FIELDS AP, SAMOLS D, GOLDTHWAIT DA: Protein kinase C isoforms in human glioblastoma cells. Clio (1992) 6(3):188–197.
  • ••This paper is one of the first reportsdescribing the expression of PKC isozymes in glioblastomas.
  • BALTUCH GH, DOOLEY NP, ROSTWOROWSKI KM, VILLEMURE JG, YONG VW: Protein kinase C isoform alpha overexpression in C6 glioma cells and its role in cell proliferation. Neurooncol (1995) 24(3):241–250.
  • MANDIL R, ASHKENAZI E, BLASS M et al.: Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells. Cancer Res. (2001) 61(11):4612–4619.
  • SHEN L, GLAZER RI: Induction of apoptosis in glioblastoma cells by inhibition of protein kinase C and its association with the rapid accumulation of p53 and induction of the insulin-like growth factor-1-binding protein-3. Biochem. Pharmacol (1998) 55(10):1711–1719.
  • SATO K, ISHIKAWA K, UI M, OKAJIMA F: Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells. Brain Res. Mol Brain Res. (1999) 74(1-2):182–189.
  • AUGUSTE P, GURSEL DB, LEMIERE S et al.: Inhibition of fibroblast growth factor/ fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms. Cancer Res. (2001) 61(4):1717–1726.
  • COSTANZI-STRAUSS E, STRAUSS BE, NAVIAUX RK, HAAS M: Restoration of growth arrest by pl6INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines. Exp. Cell Res. (1998) 238(1):51–62.
  • KOMINSKY S, JOHNSON HM, BRYAN G et al.: IFNgamma inhibition of cell growth in glioblastomas correlates with increased levels of the cyclin dependent kinase inhibitor p21WAF1/CIP 1. Oncogene (1998) 17(23):2973–2979.
  • MISHIMA K, OHNO S, SHITARA N, YAMAOKA K, SUZUKI K: Opposite effects of the overexpression of protein kinase C gamma and delta on the growth properties of human glioma cell line U251 MG. Biochem. Biophys. Res. Commun. (1994) 201(1):363–372.
  • BRODIE C, KUPERSTEIN I, ACS P, BLUMBERG PM: Differential role of specific PKC isoforms in the proliferation of glial cells and the expression of the astrocytic markers GFAP and glutamine synthetase. Brain Res. Mol Brain Res. (1998) 56(1-2):108–117.
  • HOVELMANN S, BECKERS TL, SCHMIDT M: Molecular alterations in apoptotic pathways after PKB/ Akt-mediated chemoresistance in NCI H460 cells. Br. Cancer (2004) 90(12):2370–2377.
  • TANG D, OKADA H, RULAND J et al: Akt is activated in response to an apoptotic signal. J. Biol. Chem. (2001) 276(32):30461–30466.
  • SHINOHARA H, KAYAGAKI N, YAGITA H et al.: A protective role of PKCepsilon against TNF-related apoptosis-inducing ligand (TRAM-induced apoptosis in glioma cells. Biochem. Biophys. Res. Commun. (2001) 284(5):1162–1167.
  • BLASS M, KRONFELD I, KAZIMIRSKY G, BLUMBERG PM, BRODIE C: Tyrosine phosphorylation of protein kinase Cdelta is essential for its apoptotic effect in response to etoposide. Mol Cell. Biol. (2002) 22(1):182–195.
  • KRONFELD I, KAZIMIRSKY G, LORENZO PS et al.: Phosphorylation of protein kinase Cdelta on distinct tyrosine residues regulates specific cellular functions. J. Biol. Chem. (2000) 275(45):35491–35498.
  • VANMETER TE, ROOPRAI HK, KIBBLE MM et al: The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. Neurooncol (2001) 53(2):213–235.
  • PARK MJ, PARK IC, HUR JH et al: Protein kinase C activation by phorbol ester increases in vitro invasion through regulation of matrix metalloproteinases/ tissue inhibitors of metalloproteinases system in D54 human glioblastoma cells. Neurosci. Lett. (2000) 290(3):201–204.
  • CHO KK, MIKKELSEN T, LEE YJ et al: The role of protein kinase Calpha in U-87 glioma invasion. Int. I Dev. Neurosci. (1999) 17(5-6):447–461.
  • •This paper conclusively demonstrates the regulation of glioma invasion by PKCa.
  • KERMORGANT S, ZICHA D, PARKER PJ: PKC controls HGF-dependent c-Met traffic, signalling and cell migration. EMBO. J. (2004) 23(19):3721–3734.
  • KUNKEL P, MULLER S, SCHIRMACHER P et al.: Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas. Neuro-oncol. (2001) 3(2):82–88.
  • CHATTOPADHYAY N, TFELT-HANSEN J, BROWN EM: PKC, p42/44 MAPK and p38 MAPK regulate hepatocyte growth factor secretion from human astrocytoma cells. Broth Res. Mol Brain Res. (2002) 102(1-2):73–82.
  • IVASKA J, WHELAN RD, WATSON R, PARKER PJ: PKC epsilon controls the traffic of betal integrins in motile cells. Embo. J. (2002) 21(103608–3619.
  • BESSON A, WILSON TL, YONG VW: The anchoring protein RACK1 links protein kinase Cepsilon to integrin beta chains. Requirements for adhesion and motility. J. Biol. Chem. (2002) 277(24):22073–22084.
  • BESSON A, DAVY A, ROBBINS SM, YONG VW: Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells. Oncogene (2001) 20(50):7398–7407.
  • ESTEVE PO, CHICOINE E, ROBLEDO O et al.: Protein kinase C-zeta regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-alpha in glioma cells via NF-kappa B. J. Biol. Chem. (2002) 277(38):35150–35155.
  • YOSHIJI H, KURIYAMA S, WAYS DK et al.: Protein kinase C lies on the signaling pathway for vascular endothelial growth 59(17):4413–4418.
  • PAL S, CLAFFEY KP, DVORAK HF, MUKHOPADHYAY D: The von vascular permeability factor/vascular endothelial growth factor expression in renal cell carcinoma by blocking protein kinase C pathways. J. Biol. Chem. (1997) 272(44):27509–27512.
  • TEICHER BA, MENON K, ALVAREZ E et al.: Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human T98G glioblastoma multiforme xenografts. Clin. Cancer Res. (2001) 7(3):634–640.
  • WANG A, NOMURA M, PATAN S, WARE JA: Inhibition of protein kinase Calpha prevents endothelial cell migration and vascular tube formation in vitro and myocardial neovascularization in vivo. Circ. Res. (2002) 90(5):609–616
  • HARRINGTON EO, DOYLE KE, BRUNELLE JL, WARE JA: Endothelial proliferation, migration, and differentiation are blunted by conditionally expressed 271(2):499–508.
  • SHIZUKUDA Y, TANG S, YOKOTA R, WARE JA: Vascular endothelial growth factor-induced endothelial cell migration and proliferation depend on a nitric oxide-mediated decrease in protein kinase Cdelta activity. Circ. Res. (1999) 85(3):247–256.
  • HARRINGTON EO, LOFFLER J, NELSON PR et al.: Enhancement of migration by protein kinase Calpha and inhibition of proliferation and cell cycle progression by protein kinase Cdelta in capillary endothelial cells. ./. Biol. Chem. (1997) 272(10:7390–7397.
  • GOEKJIAN PG, JIROUSEK MR: Protein kinase C inhibitors as novel anticancer drugs. Expert Opin. Investig. Drugs (2001) 10(12):2117–2140.
  • •A review discussing the potential that PKC isozymes could have as chemotherapeutic targets in cancer.
  • RAMACHANDRAN C, KHATIB Z, PETKAROU A et al: Tamoxifen modulation of etoposide cytotoxicity involves inhibition of protein kinase C activity and insulin-like growth Factor II expression in brain tumor cells. Neurooncol. (2004) 67 (1-2) :19–28.
  • BURSZTAJN S, FENG JJ, NANDA A, BERMAN SA: Differential responses of human neuroblastoma and glioblastoma to apoptosis. Brain Res. Mol Brain Res. (2001) 91(1-2):57–72.
  • ZHANG W, LAW RE, HINTON DR, COULDWELL WT: Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. Cancer Lett. (1997) 120(1):31–38.
  • BEGEMANN M, KASHIMAWO SA, HEITJAN DF et al.: Treatment of human glioblastoma cells with the staurosporine derivative CGP 41251 inhibits CDC2 and CDK2 kinase activity and increases radiation sensitivity. Anti-Cancer Res. (1998) 18(442275–2282.
  • COULD WELL WT, HINTON DR, HE S et al: Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines. FEBS Lett. (1994) 345(1):43–46.
  • POLLACK IF, DAROSSO RC, ROBERTSON PL et al.: A Phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood. Clin. Cancer Res. (1997) 3(7):1109–1115.
  • COULD WELL WT, HINTON DR, SURNOCK AA et al: Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen. Clin. Cancer Res. (1996) 2(4):619–622.
  • PUCHNER MJ, GIESE A: Tamoxifen-resistant glioma-cell sub-populations are characterized by increased migration and proliferation. Int J. Cancer (2000) 86(4):468–473.
  • CHEN TC, SU S, FRY D, LIEBES L: Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma. Cancer (2003) 97(9 Suppl.):2363–2373.
  • HIROSE Y, BERGER MS, PIEPER RO: Abrogation of the Chkl-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Cancer Res. (2001) 61(15):5843–5849.
  • BREDEL M, POLLACK IF, FREUND JM, RUSNAK J, LAZO JS: Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion. ./. Neurooncol. (1999) 41(1):9–20.
  • HIROSE Y, KATAYAMA M, BERGER MS, PIEPER RO: Cooperative function of Chkl and p38 pathways in activating G2 arrest following exposure to temozolomide. ./. Neurosurg. (2004) 100(6):1060–1065.
  • POLLACK IF, KAWECKI S, LAZO JS: Blocking of glioma proliferation in vitro and in vivo and potentiating the effects of BCNU and cisplatin: UCN-01, a selective protein kinase C inhibitor. J. Neurosurg. (1996) 84(6):1024–1032.
  • KORTMANSKY J, SCHWARTZ GK: Bryostatin-1: a novel PKC inhibitor in clinical development. Cancer Invest. (2003) 21(6):924–936.
  • PFISTER DG, MCCAFFREY J, ZAHALSKY AJ et al: A Phase II trial of bryostatin-1 in patients with metastatic or recurrent squamous cell carcinoma of the head and neck. Invest. New Drugs (2002) 20(1):123–127.
  • HAAS NB, SMITH M, LEWIS N et al: Weekly bryostatin-1 in metastatic renal cell carcinoma: a Phase II study. Clin. Cancer Res. (2003) 9(1):109–114.
  • BARYZA JL, BRENNER SE, CRASKE ML, MEYER T, WENDER PA: Simplified analogs of bryostatin with anticancer activity display greater potency for translocation of PKCdelta-GFP. Chem. Biol. (2004) 11(9):1261–1267.
  • KOBAYASHI E, ANDO K, NAKANO H et al.: Calphostins (UCN-1028), novel and specific inhibitors of protein kinase C. I. Fermentation, isolation, physico-chemical properties and biological activities. Antibiot. (Tokyo) (1989) 42(10):1470–1474.
  • KOBAYASHI E, ANDO K, NAKANO H, TAMAOKI T: UCN-1028A, a novel and specific inhibitor of protein kinase C, from Cladosporium. Antibiot. (Tokyo) (1989) 42(1):153–155.
  • ACEVEDO-DUNCAN M, PEARLMAN J, ZACHARIAH B: Sensitivity of human glioma U-373MG cells to radiation and the protein kinase C inhibitor, calphostin C. Cell Prolff (2001) 34(1):31–41.
  • IKEMOTO H, TANI E, OZAKI I, KITAGAWA H, ARITA N: Calphostin C-mediated translocation and integration of Box into mitochondria induces cytochrome c release before mitochondrial dysfunction. Cell Death Differ. (2000) 7(6):511–520.
  • DA ROCHA AB, MANS DR, LENZ G et al: Protein kinase C-mediated in vitro invasion of human glioma cells through extracellular-signal-regulated kinase and ornithine decarboxylase. Pathobiology (2000) 68(3):113–123.
  • ENGELHARD HH: Antisense Oligodeoxynucleotide Technology: Potential Use for the Treatment of Malignant Brain Tumors. Cancer Control (1998) 5(2):163–170.
  • YAZAKI T, AHMAD S, CHAHLAVI A et al.: Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide. Mol Pharmacol (1996) 50(2):236–242.
  • SHEN L, DEAN NM, GLAZER RI: Induction of p53-dependent, insulin-like growth factor-binding protein-3-mediated apoptosis in glioblastoma multiforme cells by a protein kinase Calpha antisense oligonucleotide. Mol Pharmacol (1999) 55(2):396–402.
  • ADVANI R, PEETHAMBARAM P, LUM BL et al.: A Phase II trial of aprinocarsen, an antisense oligonucleotide inhibitor of protein kinase C alpha, administered as a 21-day infusion to patients with advanced ovarian carcinoma. Cancer (2004) 100(2):321–326.
  • MANI S, RUDIN CM, KUNKEL K et al.: Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer. Clin. Cancer Res. (2002) 8(4):1042–1048.
  • •This study reports a finding that suggests PKCa antisense ODNs may be effective if combined with other chemotherapeutics.
  • SONNEMANN J, GEKELER V, AHLBRECHT K et al: Down-regulation of protein kinase Ceta by antisense oligonucleotides sensitises A549 lung cancer cells to vincristine and paclitaxel. Cancer Lett. (2004) 209(2):177–185.
  • SONNEMANN J, GEKELER V, SAGRAUSKE A et al: Down-regulation of protein kinase Ceta potentiates the cytotoxic effects of exogenous tumor necrosis factor-related apoptosis-inducing ligand in PC-3 prostate cancer cells. Mol Cancer Ther. (2004) 3(7):773–781.
  • ELBASHIR SM, HARBORTH J, LENDECKEL W et al: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature (2001) 411(6836):494–498.
  • •First article to demonstrate the effectiveness of siRNA in mammalian cells.
  • YIN JQ, GAO J, SHAO R et al: siRNA agents inhibit oncogene expression and attenuate human tumor cell growth. Exp. Ther. Oncol (2003) 3(4):194–204.
  • IRIE N, SAKAI N, UEYAMA T et al: Subtype- and species-specific knockdown of PKC using short interfering RNA. Biochem. Biophys. Res. Commun. (2002) 298(5):738–743.
  • LEIRDAL M, SIOUD M: Gene-array analysis of glioma cells after treatment with an anti-PKCalpha siRNA: a general protocol. Methods Mol Biol. (2004) 252:493–500.
  • ••This article describes in detail the protocolused to assay gene expression changes following siRNA treatment in human glioblastoma cells.
  • UCHIDA H, TANAKA T, SASAKI K et al: Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo. Mol .Ther. (2004) 10(1):162–171.
  • KONNIKOVA L, KOTECKI M, KRUGER MM, COCHRAN BH: Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer (2003) 3(1):23.
  • DING Q, STEWART J, JR., OLMAN MA, KLOBE MR, GLADSON CL: The pattern of enhancement of Src kinase activity on platelet-derived growth factor stimulation of glioblastoma cells is affected by the integrin engaged../. Biol. Chem. (2003) 278(40:39882–39891.

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