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Characterization of the Role of Protein Kinase C Isozymes in Colon Carcinogenesis Using Transgenic Mouse Models

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Protein Kinase C Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 233))

Abstract

Protein kinase C (PKC) is a family of related serine/threonine lipid-dependent kinases that have been implicated in intestinal epithelial cell proliferation, apoptosis, cellular transformation, and colon carcinogenesis in rodent models and in humans (1–12). Early studies revealed that PKC activity is higher in actively proliferating colonic epithelial cells than in their quiescent counterparts (2), suggesting a role for PKC activation in proliferation of these cells. More recent studies have demonstrated that colonic epithelial cells express multiple PKC isozymes and that expression of these isozymes is differentially modulated during colon carcinogenesis (1,13–15). All of these studies indicate a direct connection between PKC and colon carcinogenesis.

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References

  1. Guan, R., Zhang, Y., Jiang, J., Baumann, C. A., Black, R. A., Baumann, G., et al. (2001) Phorbol ester-and growth factor-induced growth hormone (GH) receptor proteolysis and GH-binding protein shedding: relationship to GH receptor down-regulation. Endocrinology 142, 1137–1147.

    Article  PubMed  CAS  Google Scholar 

  2. Yamanishi, J., Takai, Y, Kaibuchi, K., Sano, K., Castagna, M., and Nishizuka, Y (1983) Synergistic functions of phorbol ester and calcium in serotonin release from human platelets. Biochem. Biophys. Res. Commun. 112, 778–786.

    Article  PubMed  CAS  Google Scholar 

  3. Saxon, M. L., Zhao, X., and Black, J. D. (1994) Activation of protein kinase C isozymes is associated with post-mitotic events in intestinal epithelial cells in situ. J. Cell Biol. 126, 747–763.

    Article  PubMed  CAS  Google Scholar 

  4. Gregorio, C. C., Repasky, E. A., Fowler, V. M., and Black, J. D. (1994) Dynamic properties of ankyrin in T lymphocytes: colocalization with spectrin and protein kinase C beta. J. Cell Biol. 125, 345–358.

    Article  PubMed  CAS  Google Scholar 

  5. Black, S. C., Fagbemi, S. O., Chi, L., Friedrichs, G. S., and Lucchesi, B. R. (1993) Phorbol ester-induced ventricular fibrillation in the Langendorff-perfused rabbit heart: antagonism by staurosporine and glibenclamide. J. Mol. Cell Cardiol. 25, 1427–1438.

    Article  PubMed  CAS  Google Scholar 

  6. Dempsey, E. C., Newton, A. C., Mochly-Rosen, D., Fields, A. P., Reyland, M. E., Insel, P. A., et al. (2000) Protein kinase C isozymes and the regulation of diverse cell responses. Am. J. Physiol. 279, L429–L438.

    CAS  Google Scholar 

  7. Dorn, G. W., Souroujon, M. C., Liron, T., Chen, C. H., Gray, M. O., Zhou, H. Z., et al. (1999) Sustained in vivo cardiac protection by a rationally designed peptide that causes epsilon protein kinase C translocation. Proc. Natl. Acad. Sci. USA 96, 12,798–12,803.

    Article  PubMed  CAS  Google Scholar 

  8. Csukai, M., Chen, C. H., De Matteis, M. A., and Mochly-Rosen, D. (1997) The coatomer protein beta’-COP, a selective binding protein (RACK) for protein kinase Cepsilon. J. Biol. Chem. 272, 29,200–29,206.

    Article  PubMed  CAS  Google Scholar 

  9. Johnson, J. A., Gray, M. O., Chen, C. H., and Mochly-Rosen, D. (1996) A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J. Biol. Chem. 271, 24,962–24,966.

    Article  PubMed  CAS  Google Scholar 

  10. Sheehy, A. M., Burson, M. A., and Black, S. M. (1998) Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am. J. Physiol. 274, L833–L841.

    PubMed  CAS  Google Scholar 

  11. Craven, P. A. and DeRubertis, F. R. (1992) Alterations in protein kinase C in 1,2-dimethylhydrazine induced colonic carcinogenesis. Cancer Res. 52, 2216–2221.

    PubMed  CAS  Google Scholar 

  12. DeRubertis, F. R. and Craven, P. A. (1987) Relationship of bile salt stimulation of colonic epithelial phospholipid turnover and proliferative activity: role of activation of protein kinase C1. Prev. Med. 16, 572–579.

    Article  PubMed  CAS  Google Scholar 

  13. La Porta, C. A. and Comolli, R. (1994) Membrane and nuclear protein kinase C activation in the early stages of diethylnitrosamine-induced rat hepatocarcinogenesis. Carcinogenesis 15, 1743–1747.

    Article  PubMed  Google Scholar 

  14. Basu, A., Mohanty, S., and Sun, B. (2001) Differential sensitivity of breast cancer cells to tumor necrosis factor-alpha: involvement of protein kinase C. Biochem. Biophys. Res. Commun. 280, 883–891.

    Article  PubMed  CAS  Google Scholar 

  15. Alele, J., Jiang, J., Goldsmith, J. F., Yang, X., Maheshwari, H. G., Black, R. A., et al. (1998) Blockade of growth hormone receptor shedding by a metalloprotease inhibitor. Endocrinology 139, 1927–1935.

    Article  PubMed  CAS  Google Scholar 

  16. Hocevar, B. A., Burns, D. J., and Fields, A. P. (1993) Identification of protein kinase C (PKC) phosphorylation sites on human lamin B. Potential role of PKC in nuclear lamina structural dynamics. J. Biol. Chem. 268, 7545–7552.

    PubMed  CAS  Google Scholar 

  17. Misra-Press, A., Fields, A. P., Samols, D., and Goldthwait, D. A. (1992) Protein kinase C isoforms in human glioblastoma cells. Glia 6, 188–197.

    Article  PubMed  CAS  Google Scholar 

  18. Frey, M. R., Leontieva, O., Watters, D. J., and Black, J. D. (2001) Stimulation of protein kinase C-dependent and-independent signaling pathways by bistratene A in intestinal epithelial cells. Biochem. Pharmacol. 61, 1093–1100.

    Article  PubMed  CAS  Google Scholar 

  19. Fields, F. O. and Thorner, J. (1991) Genetic suppression analysis of the function of a protein kinase C (PKC1 gene product) in Saccharomyces cerevisiae cell cycle progression: the SKCd mutations. Cold Spring Harb. Symp. Quant. Biol. 56, 51–60.

    PubMed  CAS  Google Scholar 

  20. Hunter, S. E., Seibenhener, M. L., and Wooten, M. W. (1995) Atypical zeta-protein kinase c displays a unique developmental expression pattern in rat brain. Brain Res. Dev. Brain Res. 85, 239–248.

    Article  PubMed  CAS  Google Scholar 

  21. Nel, A. E., Schabort, I., Rheeder, A., Bouic, P., and Wooten, M. W. (1987) Inhibition of antibodies to CD3 surface antigen and phytohemagglutinin-mediated T cellular responses by inhibiting Ca2+/phospholipid-dependent protein kinase activity with the aid of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride. J. Immunol. 139, 2230–2236.

    PubMed  CAS  Google Scholar 

  22. Berra, E., Municio, M. M., Sanz, L., Frutos, S., Diaz-Meco, M. T., and Moscat, J. (1997) Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade. Mol. Cell Biol. 17, 4346–4354.

    PubMed  CAS  Google Scholar 

  23. Frutos, S., Moscat, J., and Diaz-Meco, M. T. (1999) Cleavage of zetaPKC but not lambda/iotaPKC by caspase-3 during UV-induced apoptosis. J. Biol. Chem. 274, 10,765–10,770.

    Article  PubMed  CAS  Google Scholar 

  24. Sanz, L., Sanchez, P., Lallena, M. J., Diaz-Meco, M. T., and Moscat, J. (1999) The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 18, 3044–3053.

    Article  PubMed  CAS  Google Scholar 

  25. Cai, H., Smola, U., Wixler, V., Eisenmann-Tappe, I., Diaz-Meco, M. T., Moscat, J., et al. (1997) Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase. Mol. Cell Biol. 17, 732–741.

    PubMed  CAS  Google Scholar 

  26. Standaert, M. L., Bandyopadhyay, G., Perez, L., Price, D., Galloway, L., Poklepo-vic, A., et al. (1999) Insulin activates protein kinases C-zeta and C-lambda by an autophosphorylation-dependent mechanism and stimulates their translocation to GLUT4 vesicles and other membrane fractions in rat adipocytes. J. Biol. Chem. 274, 25,308–25,316.

    Article  PubMed  CAS  Google Scholar 

  27. Sanz-Navares, E., Fernandez, N., Kazanietz, M. G., and Rotenberg, S. A. (2001) Atypical protein kinase Czeta suppresses migration of mouse melanoma cells. Cell Growth Differ. 12, 517–524.

    PubMed  CAS  Google Scholar 

  28. Roy, H. K., Bissonnette, M., Frawley, B. P., Jr., Wali, R. K., Niedziela, S. M., Earnest, D., et al. (1995) Selective preservation of protein kinase C-zeta in the chemoprevention of azoxymethane-induced colonic tumors by piroxicam. FEBS Lett. 366, 143–145.

    Article  PubMed  CAS  Google Scholar 

  29. Hogan, B., Beddington, R., Costantini, F., and Lacy, E. (Eds.) (1994) Manipulating the Mouse Embryo: A Laboratory Manual, 2nd ed., Cold Spring Harbor Press, Cold Spring Harbor, New York.

    Google Scholar 

  30. Simon, T. C., Roth, K. A., and Gordon, J. I. (1993) Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J. Biol. Chem. 268, 18,345–18,358.

    PubMed  CAS  Google Scholar 

  31. Yoshimi, N., Wang, A., Makita, H., Suzui, M., Mori, H., Okano, Y., et al. (1994) Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat colon neoplasms induced by methylazoxymethanol acetate. Mol. Carcinog. 11, 192–196.

    Article  PubMed  CAS  Google Scholar 

  32. Murray, N. R., Davidson, L. A., Chapkin, R. S., Gustafson, W. C., Schattenberg, D. G., and Fields, A. P. (1999) Overexpression of protein kinase C betaII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. J. Cell Biol. 145, 699–711.

    Article  PubMed  CAS  Google Scholar 

  33. Murray, N. R., Weems, C., Chen, L., Leon, J., Yu, W., Davidson, L. A., et al. (2002) Protein kinase C βII and TGFβRII in δ-3 fatty acid-mediated inhibition of colon carcinogenesis. J. Cell Biol. 157, 915–920.

    Article  PubMed  CAS  Google Scholar 

  34. Kerr, J. F., Gobe, G. C., Winterford, C. M., and Harmon, B. V. (1995) Anatomical methods in cell death. Methods Cell Biol. 46, 1–27.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. The Mayo Clinic Cancer Center, Jacksonville, FL

    Alan P. Fields & Nicole R. Murray

  2. The Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX

    W. Clay Gustafson

Authors
  1. Alan P. Fields
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  2. Nicole R. Murray
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  3. W. Clay Gustafson
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, University of California at San Diego, La Jolla, CA

    Alexandra C. Newton

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© 2003 Humana Press Inc., Totowa, NJ

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Fields, A.P., Murray, N.R., Gustafson, W.C. (2003). Characterization of the Role of Protein Kinase C Isozymes in Colon Carcinogenesis Using Transgenic Mouse Models. In: Newton, A.C. (eds) Protein Kinase C Protocols. Methods in Molecular Biology™, vol 233. Humana Press. https://doi.org/10.1385/1-59259-397-6:539

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  • DOI: https://doi.org/10.1385/1-59259-397-6:539

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-068-7

  • Online ISBN: 978-1-59259-397-2

  • eBook Packages: Springer Protocols

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