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Protein Kinase C and Lung Cancer

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Protein Kinase C in Cancer Signaling and Therapy

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

The protein kinase C (PKC) family of serine/threonine kinases has been linked to the carcinogenic process of many types of human cancers including lung cancer. Lung carcinogenesis is a multistep process involving both genetic and epigenetic alterations in oncogenes and tumor suppressor genes, and changes in activation of signal transduction pathways, resulting in progressive deregulation of cell proliferation and survival mechanisms. Alterations in PKC isoform expression and/or activity have been observed in human lung cancer, and functional studies have suggested that individual PKC isoforms play distinct, sometimes opposite, effects in transformation, proliferation, and survival of human lung cancer cells. This chapter provides a brief review of current knowledge regarding PKC isoform-specific roles in the pathogenesis of human lung cancer and therapeutic potential of targeting specific PKC isoforms.

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References

  • Ahmad, S., Trepel, J. B., Ohno, S., et al. (1992). Role of protein kinase C in the modulation of multidrug resistance: Expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin. Molecular Pharmacology, 42, 1004–1009.

    PubMed  CAS  Google Scholar 

  • Akimoto, K., Mizuno, K., Osada, S., et al. (1994). A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells. The Journal of Biological Chemistry, 269, 12677–12683.

    PubMed  CAS  Google Scholar 

  • Alberg, A. J., & Samet, J. M. (2003). Epidemiology of lung cancer. Chest, 123, 21S–49S.

    Article  PubMed  Google Scholar 

  • Auberger, J., Loeffler-Ragg, J., Wurzer, W., & Hilbe, W. (2006). Targeted therapeutics in non-small cell lung cancer: Proven concepts and unfulfilled promises. Current Cancer Drug Targets, 6, 271–294.

    Article  PubMed  CAS  Google Scholar 

  • Awasthi, S., Singhal, S. S., Sharma, R., et al. (2003). Transport of glutathione-conjugates and chemotherapeutic drugs by RLIP76 (RLIP76): A novel link between G-protein and tyrosine kinase signaling and drug resistance. International Journal of Cancer, 106, 635–646.

    Article  CAS  Google Scholar 

  • Awasthi, S., Singhal, S. S., Singhal, J., et al. (2003). Role of RLIP76 in lung cancer doxorubicin resistance II. Doxorubicin transport in lung cancer by RLIP76. International Journal of Oncology, 22, 713–720.

    PubMed  CAS  Google Scholar 

  • Bae, K.-M., Wang, H., Jiang, G., et al. (2007). Protein kinase Cε is overexpressed in primary human non-small cell lung cancers and functionally required for proliferation of non-small cell lung cancer cells in a p21/Cip1-dependent manner. Cancer Research, 67, 6053–6063.

    Article  PubMed  CAS  Google Scholar 

  • Basu, A., & Sivaprasad, U. (2007). Protein kinase Cε makes the life and death decision. Cellular Signalling, 19, 1633–1642.

    Article  PubMed  CAS  Google Scholar 

  • Baxter, G., Oto, E., Daniel-Issakani, S., & Strulovici, B. (1992). Constitutive presence of a catalytic fragment of protein kinase Cε in a small cell lung carcinoma cell line. The Journal of Biological Chemistry, 267, 1910–1917.

    PubMed  CAS  Google Scholar 

  • Black, J. D. (2000). Protein kinase C-mediated regulation of the cell cycle. Frontiers Bioscience, 5, d406–d423.

    Article  CAS  Google Scholar 

  • Blumberg, P. M., Jaken, S., Konig, B., et al. (1984). Mechanism of action of the phorbol ester tumor promoters: Specific receptors for lipophilic ligands. Biochemical Pharmacology, 33, 933–940.

    Article  PubMed  CAS  Google Scholar 

  • Bruey, J. M., Ducasse, C., Bonniaud, P., et al. (2000). Hsp27 negatively regulates cell death by interacting with cytochrome c. Nature Cell Biology, 2, 645–652.

    Article  PubMed  CAS  Google Scholar 

  • Cacace, A. M., Guadagno, S. N., Krauss, R. S., et al. (1993). The epsilon isoform of protein kinase C is an oncogene when overexpressed in rat fibroblasts. Oncogene, 8, 2095–2104.

    PubMed  CAS  Google Scholar 

  • Castagna, M., Takai, Y., Kaibuchi, K., et al. (1982). Direct activation of calcium-activated, phospholipids-dependent protein kinase by tumor-promoting phorbol esters. The Journal of Biological Chemistry, 257, 7847–7851.

    PubMed  CAS  Google Scholar 

  • Chen, M. G., Chen, M., Wang, H., et al. (2008). Alterations in the expression of protein kinase C isoforms in primary human non-small cell lung cancers [abstract #5223]. In Abstracts of the Annual Meeting of American Association for Cancer Research, San Diego, 12–16, April 2008.

    Google Scholar 

  • Choi, S. H., Hyman, T., & Blumberg, P. M. (2006). Differential effect of bryostatin 1 and phorbol 12-myristate 13-acetate on HOP-92 cell proliferation is mediated by down-regulation of protein kinase Cdelta. Cancer Research, 66, 7261–7269.

    Article  PubMed  CAS  Google Scholar 

  • Clark, A. S., West, K. A., Blumberg, P. M., & Dennis, P. A. (2003). Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance. Cancer Research, 63, 780–786.

    PubMed  CAS  Google Scholar 

  • Davies, S. P., Reddy, H., Caivano, M., & Cohen, P. (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochemical Journal, 351, 95–105.

    Article  PubMed  CAS  Google Scholar 

  • Dean, N. M., McKay, R., Condon, T. P., et al. (1994). Inhibition of protein kinase C-α expression in humans A549 cells by antisense oligonucleotides inhibits induction of intracellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters. The Journal of Biological Chemistry, 269, 16416–16424.

    PubMed  CAS  Google Scholar 

  • Dean, N. M., McKay, R., Miraglia, L., et al. (1996). Inhibition of growth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C α expression. Cancer Research, 56, 3499–3507.

    PubMed  CAS  Google Scholar 

  • Deeds, L., Teodorescu, S., Chu, M., et al. (2003). A p53-independent G1 cell cycle checkpoint induced by the suppression of protein kinase C alpha and theta isoforms. The Journal of Biological Chemistry, 278, 39782–39793.

    Article  PubMed  CAS  Google Scholar 

  • Dempsey, E. C., Newton, A. C., Mochly-Rosen, D., et al. (2000). Protein kinase C isozymes and the regulation of diverse cell responses. American Journal of Physiology. Lung Cellular and Molecular Physiology, 279, L429–L438.

    PubMed  CAS  Google Scholar 

  • Ding, L., Wang, H., Lang, W., & Xiao, L. (2002). Protein kinase C-ε promotes survival of lung cancer cells by suppressing apoptosis through dysregulation of the mitochondrial caspase pathway. The Journal of Biological Chemistry, 277, 35305–35313.

    Article  PubMed  CAS  Google Scholar 

  • Duran, A., Diaz-Meco, M. T., & Moscat, J. (2003). Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaB transcriptional activation. EMBO Journal, 22, 3910–3918.

    Article  PubMed  CAS  Google Scholar 

  • Erdogan, E., Lamark, T., Stallings-Mann, M., et al. (2006). Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Cι. The Journal of Biological Chemistry, 281, 28450–28459.

    Article  PubMed  CAS  Google Scholar 

  • Evan, G. I., & Vousden, K. H. (2001). Proliferation, cell cycle and apoptosis in cancer. Nature, 411, 342–348.

    Article  PubMed  CAS  Google Scholar 

  • Facchini, F. M., & Spiro, S. G. (1999). Chemotherapy in small-cell lung cancer. In C. Brambilla & E. Brambilla (Eds.), Lung Biology in Health and Disease: Lung Tumors (Vol. 124, pp. 611–630). New York: Marcel Dekker.

    Google Scholar 

  • Felber, M., Sonnemann, J., & Beck, J. F. (2007). Inhibition of novel protein kinase C-epsilon augments TRAIL-induced cell death in A549 lung cancer cells. Pathology Oncology Research, 13, 295–301.

    Article  PubMed  CAS  Google Scholar 

  • Fields, A. P., & Regala, R. P. (2007). Protein kinase Cι: Human oncogenes, prognostic marker and therapeutic target. Pharmacological Research, 55, 487–497.

    Article  PubMed  CAS  Google Scholar 

  • Frederick, L. A., Matthews, J. A., Jamieson, L., et al. (2008). Matrix metalloproteinase-10 is a critical effector of protein kinase Cι-Par6α-mediated lung cancer. Oncogene, 27, 4841–4853.

    Article  PubMed  CAS  Google Scholar 

  • Galvez, A. S., Duran, A., Linares, J. F., Pathrose, P., Castilla, E. A., Abu-Baker, S., et al. (2009). PKCzeta represses the IL-6 promoter and impairs tumorigenesis in vivo. Molecular and Cellular Biology, 29, 104–115.

    Article  PubMed  CAS  Google Scholar 

  • Graff, J. R., McNulty, A. M., Hanna, K. R., et al. (2005). The protein kinase Cβ-selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Research, 65, 7462–7469.

    Article  PubMed  CAS  Google Scholar 

  • Griner, E. M., & Kazanietz, M. G. (2007). Protein kinase C and other diacylglycerol effectors in cancer. Nature Reviews. Cancer, 7, 281–294.

    Article  PubMed  CAS  Google Scholar 

  • Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70.

    Article  PubMed  CAS  Google Scholar 

  • Hanauske, A., Oberscchmidt, O., Hanauske-Abel, H., et al. (2007). Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in vitro soft-agar cloning experiments. Investigational New Drugs, 25, 205–210.

    Article  PubMed  CAS  Google Scholar 

  • Hannun, Y. A. (1997). Apoptosis and the dilemma of cancer chemotherapy. Blood, 89, 1845–1853.

    PubMed  CAS  Google Scholar 

  • Hecht, S. S. (1999). Tobacco smoke carcinogens and lung cancer. Journal of the National Cancer Institute, 91, 1194–1210.

    Article  PubMed  CAS  Google Scholar 

  • Herbst, R. S., Oh, Y., Wagle, A., et al. (2007). Enzastaurin, a protein kinase Cβ-selective inhibitor, and its potential application as an anticancer agent in lung cancer. Clinical Cancer Research, 13, 4641s–4646s.

    Article  CAS  Google Scholar 

  • Heusch, W. L., & Maneckjee, R. (1998). Signalling pathways involved in nicotine regulation of apoptosis of human lung cancer cells. Carcinogenesis, 19, 551–556.

    Article  PubMed  CAS  Google Scholar 

  • Hurbin, A., Coll, J. L., Dubrez-Daloz, L., et al. (2005). Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells. The Journal of Biological Chemistry, 280, 19757–19767.

    Article  PubMed  CAS  Google Scholar 

  • Jaken, S., & Parker, P. J. (2000). Protein kinase C binding partners. BioEssays, 22, 245–254.

    Article  PubMed  CAS  Google Scholar 

  • Jakowlew, S. B., Mariano, J. M., & You, L. (1997). Effects of transforming growth factor-β 1 and phorbol ester on PAI-1 and PA gene in human lung cancer cell. Growth Factors, 14, 177–197.

    Article  PubMed  CAS  Google Scholar 

  • Jemal, A., Siegel, R., Ward, E., et al. (2008). Cancer Statistics, 2008. CA: A Cancer Journal for Clinicians, 58, 71–96.

    Article  Google Scholar 

  • Jin, Z., Gao, F., Flagg, T., & Deng, X. (2004). Tobacco-specific nitrosamine NNK promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation. The Journal of Biological Chemistry, 279, 40209–40219.

    Article  PubMed  CAS  Google Scholar 

  • Jin, Z., Xin, M., & Deng, X. (2005). Survival function of PKCι as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated Bad kinase. The Journal of Biological Chemistry, 280, 16045–16052.

    Article  PubMed  CAS  Google Scholar 

  • Joberty, G., Petersen, C., Gao, L., & Macara, I. G. (2000). The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature Cell Biology, 2, 531–539.

    Article  PubMed  CAS  Google Scholar 

  • Josen, K., Siegel, R., & Kamp, D. (2002). Incidence and etiology. In A. B. Weitberg (Ed.), Cancer of the Lung (pp. 3–34). Totowa: Humana Press.

    Google Scholar 

  • Kim, E.-H., Lee, H.-J., Lee, D.-H., et al. (2007). Inhibition of heat shock protein 27-mediated resistance to DNA damaging agents by a novel PKCδ-V5 heptapeptide. Cancer Research, 67, 6333–6341.

    Article  PubMed  CAS  Google Scholar 

  • Kovac, J., Oster, H., & Leitges, M. (2007). Expression of the atypical protein kinase C (aPKC) isoforms iota/lambda and zeta during mouse embryogenesis. Gene Expression Patterns, 7, 187–196.

    Article  PubMed  CAS  Google Scholar 

  • Lahn, M., McClelland, P., Ballard, D., et al. (2006). Immunohistochemical detection of protein kinase C-beta (PKC-β) in tumour specimens of patients with non-small cell lung cancer. Histopathology, 49, 426–445.

    Article  Google Scholar 

  • Lahn, M., Su, C., Li, S., et al. (2004). Expression levels of protein kinase C-alpha in non-small-cell lung cancer. Clinical Lung Cancer, 6, 184–189.

    Article  PubMed  CAS  Google Scholar 

  • Lee, Y.-J., Lee, D.-H., Cho, C.-K., et al. (2005). HSP25 inhibits protein kinase Cδ-mediated cell death through direct interaction. The Journal of Biological Chemistry, 280, 18108–18119.

    Article  PubMed  CAS  Google Scholar 

  • Lin, D., Edwards, A. S., Fawcett, J. P., et al. (2000). A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signaling and cell polarity. Nature Cell Biology, 2, 540–547.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., Wang, B., Wang, J., et al. (2009). Down-regulation of PKCζ expression inhibits chemotaxis signal transduction in human lung cancer cells. Lung Cancer, 63, 210–218.

    Article  PubMed  Google Scholar 

  • Lynch, T. J., Raju, R., Lind, M., et al. (2003). Randomized phase III trial of chemotherapy and antisense oligonucleotide LY900003 (ISIS 3521) in patients with advanced NSCLC: Initial report. Proceedings of the American Society of Clinical Oncology, 22, 623 [abstract 2504].

    Google Scholar 

  • Mai, H., May, W. S., Gao, F., et al. (2003). A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. The Journal of Biological Chemistry, 278, 1886–1891.

    Article  PubMed  CAS  Google Scholar 

  • Mao, M., Fang, X., Lu, Y., et al. (2000). Inhibition of growth-factor-induced phosphorylation and activation of protein kinase B/Akt by atypical protein kinase C in breast cancer cells. Biochemical Journal, 352, 475–482.

    Article  PubMed  CAS  Google Scholar 

  • Mills, N. E., Fishman, C. L., Scholes, J., et al. (1995). Detection of K-ras oncogene mutations in bronchoalveolar lavage fluid for lung cancer diagnosis. Journal of the National Cancer Institute, 87, 1056–1060.

    Article  PubMed  CAS  Google Scholar 

  • Minna, J. D., Roth, J. A., & Gazdar, A. F. (2002). Focus on lung cancer. Cancer Cell, 1, 49–52.

    Article  PubMed  CAS  Google Scholar 

  • Mischak, H., Goodnight, J., Kolch, W., et al. (1999). Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity. The Journal of Biological Chemistry, 268, 6090–6096.

    Google Scholar 

  • Morgillo, F., Martinelli, E., Troiani, T., et al. (2008). Sequence-dependent, synergistic antiproliferative and proapoptotic effects of the combination of cytotoxic drugs and enzastaurin, a protein kinase Cβ inhibitor in non-small cell lung cancer cells. Molecular Cancer Therapeutics, 7, 1698–1707.

    Article  PubMed  CAS  Google Scholar 

  • Mustafi, R., Cerda, S., Chumsangsri, A., et al. (2006). Protein kinase-zeta inhibits collagen I-dependent and anchorage-independent growth and enhances apoptosis of human Caco-2 cells. Molecular Cancer Research, 4, 683–694.

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa, M., Oliva, J. L., Kothapalli, D., et al. (2005). Phorbol ester-induced G1 phase arrest selectively mediated by protein kinase Cdelta-dependent induction of p21. The Journal of Biological Chemistry, 280, 33926–33934.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima, E., Helfrich, B., Chan, D., et al. (2006). Enzastaurin, a protein kinase Cβ-selective inhibitor, inhibits the growth of SCLC and NSCLC cell lines [abstract 13138]. ASCO Annual Meeting Proceedings Part I. Journal of Clinical Oncology, 24, 13138.

    Google Scholar 

  • Newton, A. C. (2001). Protein kinase C: Structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chemical Reviews, 101, 2353–2364.

    Article  PubMed  CAS  Google Scholar 

  • Newton, A. C. (2003). Regulation of the ABC kinases by phosphorylation: Protein kinase C as a paradigm. Biochemical Journal, 370, 361–371.

    Article  PubMed  CAS  Google Scholar 

  • Nishizuka, Y. (1995). Protein kinase C and lipid signaling for sustained cellular responses. FASEB Journal, 9, 484–496.

    PubMed  CAS  Google Scholar 

  • Oliva, J. L., Caino, M. C., Senderowicz, A. M., & Kazanietz, M. G. (2008). S-Phase-specific activation of PKC alpha induces senescence in non-small cell lung cancer cells. The Journal of Biological Chemistry, 283, 5466–5476.

    Article  PubMed  CAS  Google Scholar 

  • Osada, H., & Takahashi, T. (2002). Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene, 21, 7421–7434.

    Article  PubMed  CAS  Google Scholar 

  • Pardo, O. E., Arcaro, A., Salerno, G., et al. (2002). Fibroblast growth factor-2 induces translational regulation Bcl-XL and Bcl-2 via a MEK-dependent pathway: Correlation with resistance to etoposide-induced apoptosis. The Journal of Biological Chemistry, 277, 12040–12046.

    Article  PubMed  CAS  Google Scholar 

  • Pardo, O. E., Lesay, A., Arcaro, A., et al. (2003). Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells. Molecular and Cellular Biology, 23, 7600–7610.

    Article  PubMed  CAS  Google Scholar 

  • Pardo, O. E., Wellbrock, C., Khanzada, U. K., et al. (2006). EGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCε B-Raf and S6K2. EMBO Journal, 25, 3078–3088.

    Article  PubMed  CAS  Google Scholar 

  • Paz-Ares, L., Douillard, J. Y., Koralewski, P., et al. (2006). Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-α antisense oligonucleotide, in patients with advanced stage non-small cell lung cancer. Journal of Clinical Oncology, 24, 1428–1434.

    Article  PubMed  CAS  Google Scholar 

  • Perletti, G., Folini, M., Lin, H. C., et al. (1996). Overexpression of protein kinase C epsilon is oncogenic in rat colonic epithelial cells. Oncogene, 12, 847–854.

    PubMed  CAS  Google Scholar 

  • Persaud, S. D., Hoang, V., Huang, J., & Basu, A. (2005). Involvement of proteolytic activation of PKCδ in cisplatin-induced apoptosis in human small cell lung cancer H69 cells. International Journal of Oncology, 27, 149–154.

    PubMed  CAS  Google Scholar 

  • Quigley, R. L., Shafer, S. H., & Williams, C. L. (1998). Regulation of integrin-mediated adhesion by muscarinic acetylcholine receptors and protein kinase C in small cell lung carcinoma. Chest, 114, 839–846.

    Article  PubMed  CAS  Google Scholar 

  • Rane, M. J., Pan, Y., Singh, S., et al. (2003). Heat shock protein 27 controls apoptosis by regulating Akt activation. The Journal of Biological Chemistry, 278, 27828–27835.

    Article  PubMed  CAS  Google Scholar 

  • Rathore, R., & Weitberg, A. B. (2002). Small-cell lung cancer. In A. B. Weitberg (Ed.), Cancer of the Lung (pp. 3–34). Totowa: Humana Press.

    Google Scholar 

  • Regala, R. P., Thompson, E. S., & Fields, A. P. (2008). Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Research, 68, 5888–5895.

    Article  PubMed  CAS  Google Scholar 

  • Regala, R. P., Weems, C., Jamieson, L., et al. (2005a). Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Research, 65, 8905–8911.

    Article  PubMed  CAS  Google Scholar 

  • Regala, R. P., Weems, C., Jamieson, L., et al. (2005b). Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. The Journal of Biological Chemistry, 280, 31109–31115.

    Article  PubMed  CAS  Google Scholar 

  • Ritch, P., Rudin, C. M., Bitran, J. D., et al. (2006). Phase II study of PKC-alpha antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer, 52, 173–180.

    Article  PubMed  Google Scholar 

  • Ruotsalainen, T., Joensuu, H., Mattson, K., & Salven, P. (2002). High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Cancer Epidemiology, Biomarkers and Prevention, 11, 1492–1495.

    PubMed  CAS  Google Scholar 

  • Schuller, H. M. (1994). Carbon dioxide potentiates the mitogenic effects of nicotine and its carcinogenic derivative, NNK, in normal and neoplastic neuroendocrine lung cells via stimulation of autocrine and protein kinase C-dependent mitogenic pathways. Neurotoxicology, 15, 877–886.

    PubMed  CAS  Google Scholar 

  • Sekido, Y., Fong, K. M., & Minna, J. D. (2003). Molecular genetics of lung cancer. Annual Review of Medicine, 54, 73–87.

    Article  PubMed  CAS  Google Scholar 

  • Seufferlein, T., & Rozengurt, E. (1996). Galanin, neurotensin, and phorbol esters rapidly stimulate activation of mitogen-activated protein kinase in small cell lung cancer cells. Cancer Research, 56, 5758–5764.

    PubMed  CAS  Google Scholar 

  • Singhal, S. S., Wickramarachchi, D., Singhal, J., et al. (2006). Determinants of differential doxorubicin sensitivity between SCLC and NSCLC. FEBS Letters, 580, 2258–2264.

    Article  PubMed  CAS  Google Scholar 

  • Slebos, R. J., Kibbelaar, R. E., Dalesio, O., et al. (1990). K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. The New England Journal of Medicine, 323, 561–565.

    Article  PubMed  CAS  Google Scholar 

  • Soh, J. W., & Weinstein, I. B. (2003). Roles of specific isoforms of protein kinase C in the transcriptional control of cyclin D1 and related genes. The Journal of Biological Chemistry, 278, 34709–34716.

    Article  PubMed  CAS  Google Scholar 

  • Soloff, R. S., Katayama, C., Lin, M. Y., et al. (2004). Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms. Journal of Immunology, 173, 3250–3260.

    CAS  Google Scholar 

  • Stallings-Mann, M., Jamieson, L., Regala, R. P., et al. (2006). A novel small-molecular inhibitor of protein kinase Cι blocks transformed growth of non-small cell lung cancer cells. Cancer Research, 66, 1767–1774.

    Article  PubMed  CAS  Google Scholar 

  • Tapinos, N., & Rambukkana, A. (2005). Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli. Proceedings of the National Academy of Sciences of the United States of America, 102, 9188–9193.

    Article  PubMed  CAS  Google Scholar 

  • Teicher, B. A., Alvarez, E., Menon, K., et al. (2002). Antiangiogenic effects of a protein kinase Cβ-selective small molecule. Cancer Chemotherapy and Pharmacology, 49, 69–77.

    Article  PubMed  CAS  Google Scholar 

  • Teicher, B. A., Menon, K., Alvarez, E., et al. (2001). Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in murine lewis lung carcinoma and human Calu-6 non-small-cell lung carcinoma xenografts. Cancer Chemotherapy and Pharmacology, 48, 473–480.

    Article  PubMed  CAS  Google Scholar 

  • Tekle, C., Giovannetti, E., Sigmond, J., et al. (2008). Molecular pathways involved in the synergistic interaction of the PKC beta inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cells. British Journal of Cancer, 99, 750–759.

    Article  PubMed  CAS  Google Scholar 

  • Vaux, D. L., & Korsmeyer, S. J. (1999). Cell death in development. Cell, 96, 245–254.

    Article  PubMed  CAS  Google Scholar 

  • Villalona-Calero, M. A., Ritch, P., Figueroa, J. A., et al. (2004). A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer. Clinical Cancer Research, 10, 6086–6093.

    Article  PubMed  CAS  Google Scholar 

  • Volm, M., & Pommerenke, E. W. (1995). Associated expression of protein kinase C with resistance to doxorubicin in human lung cancer. Anticancer Research, 15, 463–466.

    PubMed  CAS  Google Scholar 

  • Wang, X. Y., Repasky, E., & Liu, H. T. (1999). Antisense inhibition of protein kinase Calpha reverses the transformed phenotype in human lung carcinoma cells. Experimental Cell Research, 250, 253–263.

    Article  PubMed  CAS  Google Scholar 

  • Way, K. J., Chou, E., & King, G. L. (2000). Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol, 21, 181–187.

    Article  CAS  Google Scholar 

  • Way, D. K., Posekany, K., deVente, J., et al. (1994). Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation. Cell Growth and Differentiation, 5, 1195–1203.

    Google Scholar 

  • Webb, B. L., Lindsay, M. A., Seybold, J., et al. (1997). Identification of the protein kinase C isoenzymes in human lung and airways smooth muscle at the protein and mRNA level. Biochemical Pharmacology, 54, 199–205.

    Article  PubMed  CAS  Google Scholar 

  • Weitberg, A. B. (2002). Cancer of the lung. Totowa: Humana Press.

    Google Scholar 

  • Xiao, L. (2006). Lung cancer. In M. S. Runge & C. Patterson (Eds.), Principles in Molecular Medicine (2nd ed., pp. 736–742). Totowa: Humana Press.

    Chapter  Google Scholar 

  • Xin, M., Gao, F., May, W. S., Flagg, T., & Deng, X. (2007). Protein kinase Czeta abrogates the proapoptotic function of Bax through phorylation. The Journal of Biological Chemistry, 282, 21268–21277.

    Article  PubMed  CAS  Google Scholar 

  • Xu, L., & Deng, X. (2006). Protein kinase Cι promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of μ- and m-calpains. The Journal of Biological Chemistry, 281, 4457–4466.

    Article  PubMed  CAS  Google Scholar 

  • Yan, S., & Wenner, C. E. (2001). Modulation of cyclin D1 and its signaling components by the phorbol ester TPA and the tyrosine phosphatase inhibitor vanadate. Journal of Cellular Physiology, 186, 338–349.

    Article  PubMed  CAS  Google Scholar 

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Xiao, L. (2010). Protein Kinase C and Lung Cancer. In: Kazanietz, M. (eds) Protein Kinase C in Cancer Signaling and Therapy. Current Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-543-9_19

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  • DOI: https://doi.org/10.1007/978-1-60761-543-9_19

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