Current Concepts of Tumor Promotion by Phorbol Esters and Related Compounds

  • Catherine A. O’Brian
  • Rob M. Liskamp
  • John P. Arcoleo
  • W.-L. Wendy Hsiao
  • Gerard M. Housey
  • I. Bernard Weinstein
Part of the New Horizons in Therapeutics book series (NHTH)

Abstract

Studies of carcinogenesis on mouse skin have shown that the mechanism of carcinogenesis clearly involves at least two qualitatively distinct stages (Weinstein, 1981a; Weinstein et al., 1982, and references therein). Initiation, the first stage in the two-stage model, is rapid and apparently irreversible. The observed molecular actions of initiators appear to be rapid and irreversible, since several initiators of carcinogenesis or their metabolites are electrophiles that covalently modify DNA in vivo. The second stage, promotion, is a slow and often reversible process during which initiated cells become neoplastic. Promotion is also distinguished from initiation at the molecular level, since certain tumor promoters do not bind covalently to cellular DNA but do bind reversibly to cell membrane receptors. The two-stage mouse skin carcinogenesis model has been used as a paradigm for studies on multistage carcinogenesis in several other systems. Evidence that hepatocellular cancer, bladder cancer, colon cancer, and breast cancer also proceed via processes analogous to initiation and promotion has been reviewed elsewhere (Slaga et al., 1978; Weinstein et al., 1981b). The concept of promotion appears to be especially relevant to an understanding of the causation of human breast cancer (Weinstein et al., 1981b).

Keywords

Estrogen Oncol Psoriasis Acetylcholine Indole 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahmad, Z., Lee, F. T., DePaoli-Roach, A., and Roach, P. J., 1984, Phosphorylation of glycogen synthase by the Ca2+ and phospholipid-activated protein kinase (protein kinase C), J. Biol Chem. 259:8743–8747.PubMedGoogle Scholar
  2. Arcoleo, J. P., and Weinstein, L B., 1985, Activation of protein kinase C by tumor promoting phorbol esters, teleocidin, and aplysiatoxin in the absence of added calcium, Carcinogenesis 6:213–217.PubMedCrossRefGoogle Scholar
  3. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321.PubMedCrossRefGoogle Scholar
  4. Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y., 1982, Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters, J. Biol. Chem 257:7847–7851.PubMedGoogle Scholar
  5. Coezy, E., Borgna, J. L., and Rochefort, H., 1982, Correlation between binding to estrogen receptor and inhibition of cell growth, Cancer Res. 42:317–323.PubMedGoogle Scholar
  6. Couturier, A., Bazgar, S., and Castagna, M., 1984, Further characterization of tumor promoter-mediated activation of protein kinase C, Biochem. Biophys. Res. Commun. 121:448–455.PubMedCrossRefGoogle Scholar
  7. Dicker, P., and Rozengurt, E., 1978, Stimulation of DNA synthesis by tumor promoter and pure mitogenic factors, Nature 276:723–726.PubMedCrossRefGoogle Scholar
  8. Donnelly, T. E., and Jensen, R., 1983, Effect of fluphenazine on the stimulation of calcium-sensitive, phospholipid-dependent protein kinase by TPA, Life Sci. 33:2247–2253.PubMedCrossRefGoogle Scholar
  9. Horowitz, A. D., Fujiki, H., Weinstein, I. B., Jeffrey, A., Okin, E., Moore, R. E., and Sugimura, T., 1983, Comparative effects of aplysiatoxin, debromoaplysiatoxin, and teleocidin on receptor binding and phospholipid metaboUsm, Cancer Res. 43:1529–1535.PubMedGoogle Scholar
  10. Hsiao, W.-L. W., Gattoni-Celli, S., and Weinstein, LB., 1984, Oncogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promoters. Science 226:552–555.PubMedCrossRefGoogle Scholar
  11. Hunter, T., Ling, N., and Cooper, J. A., 1984, Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane, Nature 311:480–483.PubMedCrossRefGoogle Scholar
  12. Kikkawa, U., Takai, Y., Minakuchi, R., Inohara, S., and Nishizuka, Y., 1982, Calcium-activated, phospholipid-dependent protein kinase from rat brain, J. Biol. Chem. 257:13341–13348.PubMedGoogle Scholar
  13. Lam, H.-Y. P., 1984, Tamoxifen is a calmoduHn antagonist in the activation of a cA,P phosphodiesterase, Biochem. Biophys. Res. Commun. 118:27–32.PubMedCrossRefGoogle Scholar
  14. Lippman, M. E., Bolan, G., and Huff, K. K., 1976, The effects of estrogens and antiestrogens on hormone responsive human breast cancer in long term tissue culture. Cancer Res. 36:4595–4601.PubMedGoogle Scholar
  15. Liskamp, R. M. J., Brothman, A. R., Areoleo, J. P., Miller, O. J., and Weinstein, I. B., 1985, Cellular uptake and localization of fluorescent derivatives of phorbol ester tumor promoters, Biochem. Biophys. Res. Commun. 131:920–927.Google Scholar
  16. Mori, T., Takai, Y., Minakuchi, R., Yu, B., and Nishizuka, Y., 1980, Inhibitory action of chlorpromazine, dibucaine, and other phospholipid-interacting drugs on calcium-activated, phospholipid-dependent protein kinase, J. Biol Chem. 255:8378–8380.PubMedGoogle Scholar
  17. Mouridsen, H., Palshof, T., Patterson, J., and Battersby, L., 1978, Tamoxifen in advanced breast cancer, Cancer Treat. Rev. 5:131–141.PubMedCrossRefGoogle Scholar
  18. Nishikawa, M., Sellers, J. R., Adelstein, R. S., and Hidaka, H., 1984, Protein kinase C modulates in vitro phosphorylation of the smooth muscle heavy meromyosin by myosin light chain kinase, J. Biol Chem. 259:8808–8814.PubMedGoogle Scholar
  19. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308:693–698.PubMedCrossRefGoogle Scholar
  20. O’Brian, C. A., Lawrence, D. S., Kaiser, E. T., and Weinstein, I. B., 1984, Protein kinase C phosphorylates the synthetic peptide Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val in the presence of phosphoHpid plus either Ca2+ or a phorbol ester tumor promoter, Biochem. Biophys. Res. Commun. 124:296–302.PubMedCrossRefGoogle Scholar
  21. O’Brian, C. A., Liskamp, R. M., Solomon, D. H., and Weinstein, I. B., 1985, Inhibition of protein kinase C by tamoxifen. Cancer Res. 45:2462–2465.PubMedGoogle Scholar
  22. Parker, P. J., Stabel, S., and Waterfield, M. D., 1984, Purification to homogeneity of protein kinase C from bovine brain—identity with the phorbol ester receptor, EMBO 3:953–959.Google Scholar
  23. Ramachandran, C., Yau, P., Bradburg, E. M., Shyamala, G., Yasuda, H., and Walsh, D. A., 1984, Phosphorylation of high-mobihty group proteins by the calcium-phospholipid-dependent protein kinase and the cyclic AMP dependent protein kinase, J. Biol. Chem. 259:13495–13503.PubMedGoogle Scholar
  24. Reddel, R. R., Murphy, L. C., and Sutherland, R. L., 1983, Effects of biologically active metabolites of tamoxifen on the proliferation kinetics of MCF-7 human breast cancer cells in vitro, Cancer Res. 43:4618–4624.Google Scholar
  25. Slaga, T. J., Sivak, A., and Boutwell, R. K., 1978, Mechanisms of Tumor Promotion and Cocarcinogenesis, Vol. 2, Raven Press, New York.Google Scholar
  26. Sutherland, R. L., and Murphy, L. C., 1982, Mechanisms of oestrogen antagonism by nonsteroidal antiestrogens, Mol. Cell. Endocrinol. 25:5–23.PubMedCrossRefGoogle Scholar
  27. Sutherland, R. L., Green, M. D., Hall, R. E., Reddel, R. R., and Taylor, I. W., 1983a, Tamoxifen induces accumulation of MCF-7 human mammary carcinoma cells in the G0/G1 phase of the cell cycle, Eur. J. Cancer Clin. Oncol. 19:615–621.PubMedCrossRefGoogle Scholar
  28. Sutherland, R. L., Hall, R. E., and Taylor, I. W., 1983b, Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau phase cells Cancer Res. 43:3998–4006.PubMedGoogle Scholar
  29. Weinstein, I. B., 1981a, Current concepts and controversies in chemical carcinogenesis, J. Supramol. Struct. Cell. Biochem. 17:99–120.PubMedCrossRefGoogle Scholar
  30. Weinstein, I. B., 1981b, Studies on the mechanism of action of tumor promoters and their relevance to mammary carcinogenesis, in: Cell Biology of Breast Cancer (C. M. McGrath, M. J. Brennan, and M. A. Rich, eds.). Academic Press, New York, pp. 425–450.Google Scholar
  31. Weinstein, I. B., Lee, L. S., Fisher, P. B., Mufson, R. A., and Yamasaki, H., 1979, Cellular and biochemical events associated with the action of tumor promoters, in:Naturally Occurring Carcinogens—Mutagens and Modulators of Carcinogenesis (E. C. Miller, ed.), Japan Science Press, Tokyo, pp. 301–303.Google Scholar
  32. Weinstein, I. B., Mufson, R. A., Lee, L. S., Laskin, P. B., Horowitz, A. D., and Ivanovic, v., 1980, Membrane and other biochemical effects of the phorbol esters and their relevance to tumor promotion, in: Carcinogenesis: Fundamental Mechanisms and Environmental Effects (B. Pullman, P. 0. P. Ts’O, and H. Gelboin, eds.), R. Reidel, Amsterdam, pp. 543–563.CrossRefGoogle Scholar
  33. Weinstein, I. B., Horowitz, A. D., Fisher, P., Ivanovic, V., Gattoni-Ceili, S., and Kirschmeier. P., 1982, Mechanisms of multi-stage carcinogenesis and their relevance to tumor cell heterogeneity, in:Tumor Cell Heterogeneity (A. H. Owens, D. S. Coffey, and S. B. Baylin, eds.). Academic Press, New York, pp. 261–283.Google Scholar
  34. Weinstein, I. B., Arcoleo, J. P., Backer, J., Jeffrey, A. M., Hsiao, W., Gattoni-Celli, S., and Kirschmeier, P., 1984, Molecular mechanisms of tumor promotion and multistage carcinogenesis, in:Cellular Interactions by Environmental Tumor Promoters (H. Fujiki, ed.), Japan Science Press, Toyko, pp. 59–74.Google Scholar
  35. Zwiller, J., Revel, M. O., and Melviya, A. N., 1984, Protein kinase C catalyzes the phosphorylation of guanylate cyclase in vitroy J. Biol. Chem. 260:1350–1353.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Catherine A. O’Brian
    • 1
  • Rob M. Liskamp
    • 1
  • John P. Arcoleo
    • 1
  • W.-L. Wendy Hsiao
    • 1
  • Gerard M. Housey
    • 1
  • I. Bernard Weinstein
    • 1
  1. 1.Division of Environmental Sciences, Department of Human Genetics, and Cancer Center/Institute of Cancer ResearchColumbia UniversityNew YorkUSA

Personalised recommendations