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Molecular Mechanisms of Protein Kinase C-induced Apoptosis in Prostate Cancer Cells

  • Gonzalez-Guerrico, Anatilde M. (Department of Pharmacology, University of Pennsylvania School of Medicine) ;
  • Meshki, John (Department of Pharmacology, University of Pennsylvania School of Medicine) ;
  • Xiao, Liqing (Department of Pharmacology, University of Pennsylvania School of Medicine) ;
  • Benavides, Fernando (Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division) ;
  • Conti, Claudio J. (Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division) ;
  • Kazanietz, Marcelo G. (Department of Pharmacology, University of Pennsylvania School of Medicine)
  • Published : 2005.11.30
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Abstract

Protein kinase C (PKC) isozymes, a family of serine-threonine kinases, are important regulators of cell proliferation and malignant transformation. Phorbol esters, the prototype PKC activators, cause PKC translocation to the plasma membrane in prostate cancer cells, and trigger an apoptotic response. Studies in recent years have determined that each member of the PKC family exerts different effects on apoptotic or survival pathways. $PKC{\delta}$, one of the novel PKCs, is a key player of the apoptotic response via the activation of the p38 MAPK pathway. Studies using RNAi revealed that depletion of $PKC{\delta}$ totally abolishes the apoptotic effect of the phorbol ester PMA. Activation of the classical $PKC{\alpha}$ promotes the dephosphorylation and inactivation of the survival kinase Akt. Studies have assigned a pro-survival role to $PKC{\varepsilon}$, but the function of this PKC isozyme remains controversial. Recently, it has been determined that the PKC apoptotic effect in androgen-dependent prostate cancer cells is mediated by the autocrine secretion of death factors. $PKC{\delta}$ stimulates the release of $TNF{\alpha}$ from the plasma membrane, and blockade of $TNF{\alpha}$ secretion or $TNF{\alpha}$ receptors abrogates the apoptotic response of PMA. Molecular analysis indicates the requirement of the extrinsic apoptotic cascade via the activation of death receptors and caspase-8. Dissecting the pathways downstream of PKC isozymes represents a major challenge to understanding the molecular basis of phorbol ester-induced apoptosis.

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References

  1. Aggarwal, B. B. (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat. Rev. Immunol. 3, 745- 756 https://doi.org/10.1038/nri1184
  2. Ashton, A. W., Watanabe, G., Albanese, C., Harrington, E. O., Ware, J. A. and Pestell, R. G. (1999) Protein kinase Cdelta inhibition of S-phase transition in capillary endothelial cells involves the cyclin-dependent kinase inhibitor p27(Kip1). J. Biol. Chem. 274, 20805-20811 https://doi.org/10.1074/jbc.274.30.20805
  3. Black, J. D. (2000) Protein kinase C-mediated regulation of the cell cycle. Front Biosci. 5, 406-423 https://doi.org/10.2741/Black
  4. Brose, N. and Rosenmund, C. (2002) Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters. J. Cell. Sci. 115, 4399-4411 https://doi.org/10.1242/jcs.00122
  5. Cacace, A. M., Ueffing, M., Han, E. K., Marme, D. and Weinstein, I. B. (1998) Overexpression of PKCepsilon in R6 fibroblasts causes increased production of active TGFbeta. J. Cell. Physiol. 175, 314-322 https://doi.org/10.1002/(SICI)1097-4652(199806)175:3<314::AID-JCP9>3.0.CO;2-R
  6. Cadoret, A., Baron-Delage, S., Bertrand, F., Kornprost, M., Groyer, A., Gespach, C., Capeau, J. and Cherqui, G. (1998) Oncogene-induced up-regulation of Caco-2 cell proliferation involves IGF-II gene activation through a protein kinase Cmediated pathway. Oncogene 17, 877-887 https://doi.org/10.1038/sj.onc.1202013
  7. Clark, J. A., Black, A. R., Leontieva, O. V., Frey, M. R., Pysz, M. A., Kunneva, L., Woloszynska-Read, A., Roy, D. and Black, J. D. (2004) Involvement of the ERK signaling cascade in protein kinase C-mediated cell cycle arrest in intestinal epithelial cells. J. Biol. Chem. 279, 9233-9247 https://doi.org/10.1074/jbc.M312268200
  8. Cornford, P., Evans, J., Dodson, A., Parsons, K., Woolfenden, A., Neoptolemos, J. and Foster, C. S. (1999) Protein kinase C isoenzyme patterns characteristically modulated in early prostate cancer. Am. J. Pathol. 154, 137-144 https://doi.org/10.1016/S0002-9440(10)65260-1
  9. Denning, M. F., Wang, Y., Nickoloff, B. J. and Wrone-Smith, T. (1998) Protein kinase Cdelta is activated by caspase-dependent proteolysis during ultraviolet radiation-induced apoptosis of human keratinocytes. J. Biol. Chem. 273, 29995-30002 https://doi.org/10.1074/jbc.273.45.29995
  10. DeVries, T. A., Neville, M. C. and Reyland, M. E. (2002) Nuclear import of PKCdelta is required for apoptosis: identification of a novel nuclear import sequence. EMBO J, 21, 6050-6060 https://doi.org/10.1093/emboj/cdf606
  11. Emoto, Y., Manome, Y., Meinhardt, G., Kisaki, H., Kharbanda, S., Robertson, M., Ghayur, T., Wong, W. W., Kamen, R., Weichselbaum, R. and Kufe, D. (1995) Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J. 14, 6148-6156
  12. Engedal, N. and Saatcioglu, F. (2001) Ceramide-induced cell death in the prostate cancer cell line LNCaP has both necrotic and apoptotic features. Prostate 46, 289-297 https://doi.org/10.1002/1097-0045(20010301)46:4<289::AID-PROS1035>3.0.CO;2-K
  13. Fujii, T., Garcia-Bermejo, M. L., Bernabo, J. L., Caamano, J., Ohba, M., Kuroki, T., Li, L., Yuspa, S. H. and Kazanietz, M. G. (2000) Involvement of protein kinase C delta (PKCdelta) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. Lack of proteolytic cleavage of PKCdelta. J. Biol. Chem. 275, 7574-7582 https://doi.org/10.1074/jbc.275.11.7574
  14. Garcia-Bermejo, M. L., Leskow, F. C., Fujii, T., Wang, Q., Blumberg, P. M., Ohba, M., Kuroki, T., Han, K. C., Lee, J., Marquez, V. E. and Kazanietz, M. G. (2002) Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCalpha. J. Biol. Chem. 277, 645-655 https://doi.org/10.1074/jbc.M107639200
  15. Garzotto, M., Haimovitz-Friedman, A., Liao, W. C., White-Jones, M., Huryk, R., Heston, W. D., Cardon-Cardo, C., Kolesnick, R. and Fuks, Z. (1999) Reversal of radiation resistance in LNCaP cells by targeting apoptosis through ceramide synthase. Cancer Res. 59, 5194-5201
  16. Gavrielides, M. V., Frijhoff, A. F., Conti, C. J. and Kazanietz, M. G. (2004) Protein kinase C and prostate carcinogenesis: targeting the cell cycle and apoptotic mechanisms. Curr. Drug Targets 5, 431-443 https://doi.org/10.2174/1389450043345380
  17. Gonzalez-Guerrrico, A. M. and Kazanietz, M. G. (2005) Phorbol ester-induced apoptosis in prostate cancer cells via autocrine activation of the extrinsic apoptotic cascade: A key role for PKCdelta. J. Biol. Chem. in press https://doi.org/10.1074/jbc.M506767200
  18. Harada, H. and Grant, S. (2003) Apoptosis regulators. Rev. Clin. Exp. Hematol. 7, 117-138
  19. Ikezoe, T., Yang, Y., Taguchi, H. and Koeffler, H. P. (2004) JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0- tetradecanoylphorbol-13-acetate (TPA). Br. J. Cancer 90, 2017- 2024 https://doi.org/10.1038/sj.bjc.6601834
  20. Kaul, S., Anantharam, V., Yang, Y., Choi, C. J., Kanthasamy, A. and Kanthasamy, A. G. (2005) Tyrosine phosphorylation regulates the proteolytic activation of protein kinase Cdelta in dopaminergic neuronal cells. J. Biol. Chem. 280, 28721-28730 https://doi.org/10.1074/jbc.M501092200
  21. Kazanietz, M. G. (2000) Eyes wide shut: protein kinase C isozymes are not the only receptors for the phorbol ester tumor promoters. Mol. Carcinog. 28, 5-11 https://doi.org/10.1002/(SICI)1098-2744(200005)28:1<5::AID-MC2>3.0.CO;2-G
  22. Knauf, J. A., Elisei, R., Mochly-Rosen, D., Liron, T., Chen, X. N., Gonsky, R., Korenberg, J. R. and Fagin, J. A. (1999) Involvement of protein kinase Cepsilon (PKCepsilon) in thyroid cell death. A truncated chimeric PKCepsilon cloned from a thyroid cancer cell line protects thyroid cells from apoptosis. J. Biol. Chem. 274, 23414-23425 https://doi.org/10.1074/jbc.274.33.23414
  23. Lamm, M. L., Long, D. D., Goodwin, S. M. and Lee, C. (1997) Transforming growth factor-beta1 inhibits membrane association of protein kinase C alpha in a human prostate cancer cell line, PC3. Endocrinology 138, 4657-4664 https://doi.org/10.1210/en.138.11.4657
  24. Liu, B., Maher, R. J., Hannun, Y. A., Porter, A. T. and Honn, K. V. (1994) 12(S)-HETE enhancement of prostate tumor cell invasion: selective role of PKC alpha. J. Natl. Cancer Inst. 86, 1145-1151 https://doi.org/10.1093/jnci/86.15.1145
  25. Livneh, E., Shimon, T., Bechor, E., Doki, Y., Schieren, I. and Weinstein, I. B. (1996) Linking protein kinase C to the cell cycle: ectopic expression of PKC eta in NIH3T3 cells alters the expression of cyclins and Cdk inhibitors and induces adipogenesis. Oncogene 12, 1545-1555
  26. Lu, Z., Hornia, A., Jiang, Y. W., Zang, Q., Ohno, S. and Foster, D. A. (1997) Tumor promotion by depleting cells of protein kinase C delta. Mol. Cell. Biol. 17, 3418-3428
  27. McJilton, M. A., Van Sikes, C., Wescott, G. G., Wu, D., Foreman, T. L., Gregory, C. W., Weidner, D. A., Harris, F. O., Morgan, L. A., Mohler, J. L. and Terrian, D. M. (2003) Protein kinase Cepsilon interacts with Bax and promotes survival of human prostate cancer cells. Oncogene 22, 7958-7968 https://doi.org/10.1038/sj.onc.1206795
  28. Nakagawa, M., Oliva, J. L., Kothapalli, D., Fournier, A., Assoian, R. K. and Kazanietz, M. G. (2005) Phorbol ester-induced G1 phase arrest selectively mediated by protein kinase Cdeltadependent induction of p21. J. Biol. Chem. 280, 33926-33934 https://doi.org/10.1074/jbc.M505748200
  29. Nesterov, A., Lu, X., Johnson, M., Miller, G. J., Ivashchenko, Y. and Kraft, A. S. (2001) Elevated AKT activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. J. Biol. Chem. 276, 10767-10774 https://doi.org/10.1074/jbc.M005196200
  30. Newton, A. C. (2003) Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem. J. 370, 361-371 https://doi.org/10.1042/BJ20021626
  31. Parker, P. J. and Murray-Rust, J. (2004) PKC at a glance. J. Cell Sci. 117, 131-132 https://doi.org/10.1242/jcs.00982
  32. Perletti, G. P., Concari, P., Brusaferri, S., Marras, E., Piccinini, F. and Tashjian, A. H. Jr. (1998) Protein kinase cepsilon is oncogenic in colon epithelial cells by interaction with the ras signal transduction pathway. Oncogene 16, 3345-3348 https://doi.org/10.1038/sj.onc.1201871
  33. Powell, C. T., Brittis, N. J., Stec, D., Hug, H., Heston, W. D. and Fair, W. R. (1996) Persistent membrane translocation of protein kinase C alpha during 12-0-tetradecanoylphorbol-13-acetateinduced apoptosis of LNCaP human prostate cancer cells. Cell Growth Differ. 7, 419-428
  34. Powell, C. T. and Yin, L. (2005) Overexpression of PKCepsilon sensitizes LNCaP human prostate cancer cells to induction of apoptosis by bryostatin 1. Int. J. Cancer. in press
  35. Reyland, M. E., Anderson, S. M., Matassa, A. A., Barzen, K. A. and Quissell, D. O. (1999) Protein kinase C delta is essential for etoposide-induced apoptosis in salivary gland acinar cells. J. Biol. Chem. 274, 19115-19123 https://doi.org/10.1074/jbc.274.27.19115
  36. Rusnak, J. M. and Lazo, J. S. (1996) Downregulation of protein kinase C suppresses induction of apoptosis in human prostatic carcinoma cells. Exp. Cell. Res. 224, 189-199 https://doi.org/10.1006/excr.1996.0127
  37. Sharif, T. R. and Sharif, M. (1999) Overexpression of protein kinase C epsilon in astroglial brain tumor derived cell lines and primary tumor samples. Int. J. Oncol. 15, 237-243
  38. Shim, M. and Eling, T. E. (2005) Protein kinase C-dependent regulation of NAG-1/placental bone morphogenic protein/MIC- 1 expression in LNCaP prostate carcinoma cells. J. Biol. Chem. 280, 18636-18642 https://doi.org/10.1074/jbc.M414613200
  39. 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 tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15, 356-362 https://doi.org/10.1038/ng0497-356
  40. Tanaka, Y., Gavrielides, M. V., Mitsuuchi, Y., Fujii, T. and Kazanietz, M. G. (2003) Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. J. Biol. Chem. 278, 33753-33762 https://doi.org/10.1074/jbc.M303313200
  41. Wu, D., Foreman, T. L., Gregory, C. W., McJilton, M. A., Wescott, G. G., Ford, O. H., Alvey, R. F., Mohler, J. L. and Terrian, D. M. (2002a) Protein kinase cepsilon has the potential to advance the recurrence of human prostate cancer. Cancer Res. 62, 2423-2429
  42. Wu, D. and Terrian, D. M. (2002b) Regulation of caveolin-1 expression and secretion by a protein kinase cepsilon signaling pathway in human prostate cancer cells. J. Biol. Chem. 277, 40449-40455 https://doi.org/10.1074/jbc.M206270200
  43. Yang, C. and Kazanietz, M. G. (2003) Divergence and complexities in DAG signaling: looking beyond PKC. Trends Pharmacol. Sci. 24, 602-608 https://doi.org/10.1016/j.tips.2003.09.003
  44. Yin, L., Bennani-Baiti, N. and Powell, C. T. (2005) Phorbol esterinduced apoptosis of C4-2 cells requires both a unique and a redundant protein kinase C signaling pathway. J. Biol. Chem. 280, 5533-5541 https://doi.org/10.1074/jbc.M405266200
  45. Zhang, S., Lin, Z. N., Yang, C. F., Shi, X., Ong, C. N. and Shen, H. M. (2004) Suppressed NF-kappaB and sustained JNK activation contribute to the sensitization effect of parthenolide to TNF-alpha-induced apoptosis in human cancer cells. Carcinogenesis 25, 2191-2199 https://doi.org/10.1093/carcin/bgh234
  46. Zhao, X., Gschwend, J. E., Powell, C. T., Foster, R. G., Day, K. C. and Day, M. L. (1997) Retinoblastoma protein-dependent growth signal conflict and caspase activity are required for protein kinase C-signaled apoptosis of prostate epithelial cells. J. Biol. Chem. 272, 22751-22757 https://doi.org/10.1074/jbc.272.36.22751
  47. Zimmermann, K. C., Bonzon, C. and Green, D. R. (2001) The machinery of programmed cell death. Pharmacol. Ther. 92, 57- 70 https://doi.org/10.1016/S0163-7258(01)00159-0

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