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Studies on Protein Kinase C and Colon Carcinogenesis

Studies on Protein Kinase C and Colon Carcinogenesis Abstract • To further understand the molecular mechanisms of bile acid—mediated colon tumor promotion, we have examined the possible role of protein kinase C (PKC) in this process. Protein kinase C has been implicated in tumor promotion because it is the receptor for the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and mediates the action of this compound as well as that of other tumor promoters and growth factors. Our studies show that, in a manner analogous to 12-0-tetradecanoyl-phorbol-13-acetate, deoxycholic acid (DOA) can induce a time-dependent cellular redistribution of PKC as well as a concentration-dependent overexpression of the ornithine decarboxylase gene. These results taken together with our previous findings demonstrating decreased levels of PKC in human colon carcinomas compared with adjacent normal mucosa provide evidence that PKC has a role in colon carcinogenesis. (Arch Surg 1987;122:1475-1478) References 1. Bull AW, Soullier BK, Wilson PS, et al: Promotion of azoxymethane-induced intestinal cancer by high-fat diets in rats . Cancer Res 1979;39: 4956-4959. 2. Deschner EE, Long FC, Maskens AP: Relationship between dose, time and tumor yield in mouse dimethylhydrazine-induced colon tumorigenesis . Cancer Lett 1979;8:23-28.Crossref 3. Friedman E: Differential response of premalignant epithelial cell classes to phorbol ester tumor promoters and to deoxycholic acid . Cancer Res 1981;41:4588-4599. 4. Weinstein IB: Growth factors, oncogenes and multistage carcinogenesis . J Cell Biochem 1987;33:213-224.Crossref 5. Nishizuka Y: Studies and perspectives of protein kinase C . Science 1986;233:305-312.Crossref 6. 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;257:7847-7851. 7. Yuspa SH, Lichti U, Ben T, et al: Phorbol esters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures . Nature 1976;262:402-404.Crossref 8. Pegg AE, McCann PP: Polyamine metabolism and function . Am J Physiol 1982;243:C212-C221. 9. Verma AK, Pong RC, Erickson D: Involvement of protein kinase C in ornithine decarboxylase gene expression in primary culture of newborn mouse epidermal cells and in skin tumor promotion by 12-0-tetradecanoyl-phorbol-13-acetate . Cancer Res 1986;46:6149-6155. 10. Arcoleo JP, Weinstein IB: Activation of protein kinase C by tumor promoting phorbol esters, teleocidin and aplysiatoxin in the absence of added calcium . Carcinogenesis 1985;6:213-217.Crossref 11. Narisawa T, Magadia NE, Weisberger JH, et al: Promoting effects of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N-nitrosoguanidine in rats . JNCI 1974;53:1093-1095. 12. Reddy BS, Marasaw T, Weisburger JH, et al: Promoting effect of sodium deoxycholate on colon adenocarcinomas in germ-free rats . JNCI 1976;56:441-442. 13. Reddy BS, Wynder EL: Large bowel carcinogenesis: Fecal constituents of populations with diverse incidence rates of colon cancer . JNCI 1973;50:1437-1442. 14. Fitzer CJ, O'Brian CA, Guillem JG, et al: The regulation of protein kinase C by chenodeoxycholate, deoxycholate, and several structurally related bile acids . Carcinogenesis 1987;8:217-220.Crossref 15. Takano S, Matushima M, Ertürk E, et al: Early induction of rat colonic epithelia ornithine and S-adenosyl-L-methionine decarboxylase activities by N-methyl-N'-nitro-N-nitrosoguanidine or bile salts . Cancer Res 1981;41:624-628. 16. Reznikoff CA, Brankov DW, Heidelberger C: Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division . Cancer Res 1973;33:3231-3238. 17. Guillem JG, O'Brian CA, Fitzer CJ, et al: Altered levels of protein kinase C and Ca2+ -dependent protein kinases in human colon carcinomas . Cancer Res 1987;47:2036-2039. 18. Chirgwin JM, Przybyla AE, MacDonald RJ, et al: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease . Biochemistry 1979;18:5294-5299.Crossref 19. Rigby PWJ, Dieckmann M, Rhodes C, et al: Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase . Int J Mol Biol 1977;113:237-258.Crossref 20. Kahana C, Nathans D: Nucleotide sequence of murine ornithine decarboxylaze mRNA . Proc Natl Acad Sci USA 1985;82:1673-1677.Crossref 21. Kraft AS, Anderson WB: Phorbol esters increase the amount of Ca2+ phospholipid-dependent protein kinase associated with plasma membrane . Nature 1983;307:621-623.Crossref 22. Darbon J, Issandou M, Delassus F, et al: Phorbol esters induce both intracellular translocation and down-regulation of protein kinase C in MCF-7 cells . Biochem Biophys Res Commun 1986;137:1159-1166.Crossref 23. Johnson MD, Housey GM, Kirschmeier PT, et al: Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C. Mol Cell Biol, in press. 24. Craven PA, Pfanstiel J, Saito R, et al: Relationship between loss of rat colonic surface epithelium induced by deoxycholate and initiation of the subsequent proliferative response . Cancer Res 1986;46:5754-5759. 25. Horn F, Marks F, Fischer G, et al: Decreased protein kinase C activity in psoriatic versus normal epidermis . J Invest Dermatol 1987;88:220-222.Crossref 26. O'Brian CA, Liskamp RM, Solomon DH, et al: Inhibition of protein kinase C by tamoxifen . Cancer Res 1985;45:2462-2465. 27. O'Brian CA, Liskamp RM, Solomon DH, et al: Triphenylethylenes: A new class of protein kinase C inhibitors . JNCI 1986;76:1243-1246. 28. Coezy E, Borgna JL, Rochefort H: Tamoxifen and metabolites in MCF-7 cells: Correlation between binding to estrogen receptor and inhibition of cell growth . Cancer Res 1982;42:317-323. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1987.01400240123023
Publisher site
See Article on Publisher Site

Abstract

Abstract • To further understand the molecular mechanisms of bile acid—mediated colon tumor promotion, we have examined the possible role of protein kinase C (PKC) in this process. Protein kinase C has been implicated in tumor promotion because it is the receptor for the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and mediates the action of this compound as well as that of other tumor promoters and growth factors. Our studies show that, in a manner analogous to 12-0-tetradecanoyl-phorbol-13-acetate, deoxycholic acid (DOA) can induce a time-dependent cellular redistribution of PKC as well as a concentration-dependent overexpression of the ornithine decarboxylase gene. These results taken together with our previous findings demonstrating decreased levels of PKC in human colon carcinomas compared with adjacent normal mucosa provide evidence that PKC has a role in colon carcinogenesis. (Arch Surg 1987;122:1475-1478) References 1. Bull AW, Soullier BK, Wilson PS, et al: Promotion of azoxymethane-induced intestinal cancer by high-fat diets in rats . Cancer Res 1979;39: 4956-4959. 2. Deschner EE, Long FC, Maskens AP: Relationship between dose, time and tumor yield in mouse dimethylhydrazine-induced colon tumorigenesis . Cancer Lett 1979;8:23-28.Crossref 3. Friedman E: Differential response of premalignant epithelial cell classes to phorbol ester tumor promoters and to deoxycholic acid . Cancer Res 1981;41:4588-4599. 4. Weinstein IB: Growth factors, oncogenes and multistage carcinogenesis . J Cell Biochem 1987;33:213-224.Crossref 5. Nishizuka Y: Studies and perspectives of protein kinase C . Science 1986;233:305-312.Crossref 6. 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;257:7847-7851. 7. Yuspa SH, Lichti U, Ben T, et al: Phorbol esters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures . Nature 1976;262:402-404.Crossref 8. Pegg AE, McCann PP: Polyamine metabolism and function . Am J Physiol 1982;243:C212-C221. 9. Verma AK, Pong RC, Erickson D: Involvement of protein kinase C in ornithine decarboxylase gene expression in primary culture of newborn mouse epidermal cells and in skin tumor promotion by 12-0-tetradecanoyl-phorbol-13-acetate . Cancer Res 1986;46:6149-6155. 10. Arcoleo JP, Weinstein IB: Activation of protein kinase C by tumor promoting phorbol esters, teleocidin and aplysiatoxin in the absence of added calcium . Carcinogenesis 1985;6:213-217.Crossref 11. Narisawa T, Magadia NE, Weisberger JH, et al: Promoting effects of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N-nitrosoguanidine in rats . JNCI 1974;53:1093-1095. 12. Reddy BS, Marasaw T, Weisburger JH, et al: Promoting effect of sodium deoxycholate on colon adenocarcinomas in germ-free rats . JNCI 1976;56:441-442. 13. Reddy BS, Wynder EL: Large bowel carcinogenesis: Fecal constituents of populations with diverse incidence rates of colon cancer . JNCI 1973;50:1437-1442. 14. Fitzer CJ, O'Brian CA, Guillem JG, et al: The regulation of protein kinase C by chenodeoxycholate, deoxycholate, and several structurally related bile acids . Carcinogenesis 1987;8:217-220.Crossref 15. Takano S, Matushima M, Ertürk E, et al: Early induction of rat colonic epithelia ornithine and S-adenosyl-L-methionine decarboxylase activities by N-methyl-N'-nitro-N-nitrosoguanidine or bile salts . Cancer Res 1981;41:624-628. 16. Reznikoff CA, Brankov DW, Heidelberger C: Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division . Cancer Res 1973;33:3231-3238. 17. Guillem JG, O'Brian CA, Fitzer CJ, et al: Altered levels of protein kinase C and Ca2+ -dependent protein kinases in human colon carcinomas . Cancer Res 1987;47:2036-2039. 18. Chirgwin JM, Przybyla AE, MacDonald RJ, et al: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease . Biochemistry 1979;18:5294-5299.Crossref 19. Rigby PWJ, Dieckmann M, Rhodes C, et al: Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase . Int J Mol Biol 1977;113:237-258.Crossref 20. Kahana C, Nathans D: Nucleotide sequence of murine ornithine decarboxylaze mRNA . Proc Natl Acad Sci USA 1985;82:1673-1677.Crossref 21. Kraft AS, Anderson WB: Phorbol esters increase the amount of Ca2+ phospholipid-dependent protein kinase associated with plasma membrane . Nature 1983;307:621-623.Crossref 22. Darbon J, Issandou M, Delassus F, et al: Phorbol esters induce both intracellular translocation and down-regulation of protein kinase C in MCF-7 cells . Biochem Biophys Res Commun 1986;137:1159-1166.Crossref 23. Johnson MD, Housey GM, Kirschmeier PT, et al: Molecular cloning of gene sequences regulated by tumor promoters and mitogens through protein kinase C. Mol Cell Biol, in press. 24. Craven PA, Pfanstiel J, Saito R, et al: Relationship between loss of rat colonic surface epithelium induced by deoxycholate and initiation of the subsequent proliferative response . Cancer Res 1986;46:5754-5759. 25. Horn F, Marks F, Fischer G, et al: Decreased protein kinase C activity in psoriatic versus normal epidermis . J Invest Dermatol 1987;88:220-222.Crossref 26. O'Brian CA, Liskamp RM, Solomon DH, et al: Inhibition of protein kinase C by tamoxifen . Cancer Res 1985;45:2462-2465. 27. O'Brian CA, Liskamp RM, Solomon DH, et al: Triphenylethylenes: A new class of protein kinase C inhibitors . JNCI 1986;76:1243-1246. 28. Coezy E, Borgna JL, Rochefort H: Tamoxifen and metabolites in MCF-7 cells: Correlation between binding to estrogen receptor and inhibition of cell growth . Cancer Res 1982;42:317-323.

Journal

Archives of SurgeryAmerican Medical Association

Published: Dec 1, 1987

References