Skip to main content
SpringerLink
Log in

Counteractions of Retinoic Acid and Phorbol Ester Tumor Promoter Related to Changes in Protein Kinase Activities

  • Chapter
Nutrients and Cancer Prevention

Part of the book series: Experimental Biology and Medicine ((EBAM,volume 23))

Abstract

Retinoids, derivatives of vitamin A, are antagonistic toward some of the actions of phorbol ester tumor promoters (TPA) in many cell systems, and may be important as agents in cancer chemotherapy and prevention. We have been involved with studies to elucidate the effects and counteractions of retinoic acid (RA) and TPA on two key protein kinase systems known to play a role in the regulation of cell growth, differentiation, and malignant transformation: protein kinase C (PKC) and cyclic AMP-dependent protein kinase (PKA). Results indicate that RA treatment of cells causes marked changes in PKA activity, and in the PKA regulatory subunits RI and RII, and suggest an important synergism between RA and cyclic AMP to regulate cell growth and differentiation. Treatment of cells with TPA induces a rapid activation of PKC at the plasma membrane. Within 10 min TPA also causes an increase in PKA activity, and in RI and RII, in the cytosol of PYS cells. RA, when added simultaneously with TPA, negates this TPA effect on PKA. Further, prolonged TPA treatment of cells results in a loss of PKC, whereas prolonged RA treatment of some undifferentiated cell types elevates PKC activity in the cytosol. Thus, RA and TPA can elicit opposite and antagonistic effects on PKA and PKC. These changes in protein kinase activities may be involved in the antineoplastic and therapeutic actions of retinoids.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Rubin, J., and Rosen, O. (1975) Annu. Rev. Biochem. 44: 831–887.

    Article  CAS  Google Scholar 

  2. Nishizuka, Y. (1984) Nature 308: 693–698.

    Article  CAS  Google Scholar 

  3. Sporn, M., and Roberts, A. (1983) Cancer Res. 43: 3034–3040.

    CAS  Google Scholar 

  4. Jetten, A., and DeLuca, L. (1982) Carcinogenesis 7: 513–520.

    CAS  Google Scholar 

  5. Blumberg, P.M. (1980) Crit. Rev. Toxicol. 8: 153–197.

    Article  CAS  Google Scholar 

  6. Mastro, A.M. (1982) Lymphokines 6: 263–313.

    CAS  Google Scholar 

  7. Pastan, I., Johnson, G.S., and Anderson, W.B. (1975) Annu. Rev. Biochem. 44: 492–522.

    Article  Google Scholar 

  8. Whitfield, J.F.G., Boynton, A.L., and MacManus, J.P. (1979) Mol. Cell. Biochem. 27: 155–179.

    Article  CAS  Google Scholar 

  9. Cohen, P. (1982) Nature 296: 613–620.

    Article  CAS  Google Scholar 

  10. Nimmo, H.G., and Cohen, P. (1977) Adv. Cyclic Nucleotide Res. 8: 146–166.

    Google Scholar 

  11. Walter, U., Uno, I., Liu, A.Y.C., and Greengard, P. (1977) J. Biol. Chem. 252: 6494–6500.

    CAS  Google Scholar 

  12. Martin, G. (1980) Science 209: 768–776.

    Article  CAS  Google Scholar 

  13. Strickland, S., and Mandavi, V. (1978) Cell 15:393–403.

    Article  CAS  Google Scholar 

  14. Strickland, S., Smith, K., and Marotti, K. (1980) Cell 21: 347–355.

    Article  CAS  Google Scholar 

  15. Plet, A., Evain, D., and Anderson, W.B. (1982) J. Biol. Chem. 257: 889–893.

    CAS  Google Scholar 

  16. Plet, A., Gerbaud, P., Sherman, M.I., Anderson, W.B., and Evain-Brion, D. (1986) J. Cell. Physiol. 127: 341–347.

    Article  CAS  Google Scholar 

  17. Ludwig, K.W., Loewy, B., and Niles, R.M. (1980) J. Biol. Chem. 255: 5999–6002.

    CAS  Google Scholar 

  18. Olsson, I.L., and Breitman, T.R. (1982) Cancer Res. 42: 3924–3927.

    CAS  Google Scholar 

  19. Davies, P.J.A., Murtaugh, M.P., Moore, W.T., Johnson, G.S., and Lucas, D. (1985) J. Biol. Chem. 260: 5166–5174.

    CAS  Google Scholar 

  20. Murtaugh, M.P., Moore, W.T., and Davies, J.A. (1986) J. Biol. Chem. 261: 614–621.

    CAS  Google Scholar 

  21. Rogelj, S., Loewy, B., and Niles, R.M. (1984) Eur. J. Biochem. 139: 351–357.

    Article  CAS  Google Scholar 

  22. Fontana, J.A., Emler, C., Ku, K., McClung, J.K., Butcher, F.R., and Durham, J.P. (1984) J. Cell. Physiol. 120: 49–60.

    Article  Google Scholar 

  23. Abou-Issa, H., and Duruibe, V. (1986) Biochem. Biophys. Res. Commun. 135: 116–123.

    Article  CAS  Google Scholar 

  24. Abou-Issa, H., and Duruibe, V. (1988) FASEB J. 2: A859.

    Google Scholar 

  25. Evain-Brion, D., Raynaud, F., Plet, A., Laurent, P., Leduc, B., and Anderson, W. (1986) Proc. Natl. Acad. Sci. USA 83: 5272–5276.

    Article  Google Scholar 

  26. Raynaud, F., Leduc, C., Anderson, W.B., and EvainBrion, D. (1987) J. Invest. Dermatol. 89: 105–110.

    Article  CAS  Google Scholar 

  27. Raynaud, F., Gerbaud, P., Enjolras, O., Gorin, I., Anderson, W.B., and Evain-Brion, D. (1989) Lancet (in press).

    Google Scholar 

  28. Sejersen, M., Jin, T., Rahm, P., and Ringertz, N.R. (1989) Environ. Health Perspect. 80: 247–275.

    Article  CAS  Google Scholar 

  29. Chytil, F., and Ong, D.E. (1983) Adv. Nutr. Res. 5: 13–30.

    CAS  Google Scholar 

  30. Jetten, A.M., Anderson, K., Deas, M.A., Kagechika, H., Rearick, J.I., and Shudo, K. (1987) Cancer Res. 47: 3523–3530.

    CAS  Google Scholar 

  31. Petkovich, M., Brand, N.J., Krust, A., and Chambon, P. (1987) Nature 330: 444–448.

    Article  CAS  Google Scholar 

  32. Giguere, V., Ong, E.S., Segui, P., and Evans, R.M. (1987) Nature 330: 624–627.

    Article  CAS  Google Scholar 

  33. Benbrook, D., Lernhardt, E., and Pfahl, M. (1988) Nature 333: 669–673.

    Article  CAS  Google Scholar 

  34. Brand, N., Petkovich, M., Krust, A., Chambon, P., de Thé, H.D., Macchio, A., Tiollais, P., and Dejean, A. (1988) Nature 332: 850–854.

    Article  CAS  Google Scholar 

  35. Daly, A.K., and Redfern, C.P.E. (1987) Eur. J. Biochem. 168: 133–137.

    Article  CAS  Google Scholar 

  36. Takahashi, N., and Breitman, T.R. (1989) J. Biol. Chem. 264: 5159–5163.

    CAS  Google Scholar 

  37. Jungmann, R.A., and Kranias, E.G. (1977) Int. J. Biochem. 8: 819–830.

    Article  CAS  Google Scholar 

  38. Plet, A., Evain-Brion, D., Gerbaud, P., and Anderson, W.B. (1987) Cancer Res. 47: 5831–5834.

    CAS  Google Scholar 

  39. Jetten, A.M., Jetten, M.E.R., and Sherman, M. (1979) Exp. Cell Res. 124: 381–385.

    Article  CAS  Google Scholar 

  40. Roskoski, R. (1983) Methods Enzymol. 99: 3–6.

    Article  CAS  Google Scholar 

  41. Harrison, J.J., Schwoch, G., Schweppe, J.S., and Jungmann, R.A. (1982) J. Biol. Chem. 257: 13602–13609.

    CAS  Google Scholar 

  42. Murdoch, G.H., Rosenfeld, M.G., and Evans, R.H. (1982) Science 28: 1315–1317.

    Article  Google Scholar 

  43. Glukhov, A.I., Nesterova, M.V., Bukhman, V.L., and Severin, E.S. (1986) Biochemistry (Engl. Trans. Biokhimiya ) 51: 87–94.

    Google Scholar 

  44. Omori, M., and Chytil, F. (1982) J. Biol. Chem. 257: 14370–14374.

    CAS  Google Scholar 

  45. Schindler, J., and Sherman, M. (1984) Differentiation 28: 78–85.

    Article  CAS  Google Scholar 

  46. Montminy, M.R., and Bilezikjian, L.M. (1987) Nature 328: 175–178.

    Article  CAS  Google Scholar 

  47. Thomas, T.P., Talwar, H.S., and Anderson, W.B. (1988) Cancer Res. 48: 1910–1919.

    CAS  Google Scholar 

  48. Kraft, A.S., and Anderson, W.B. (1983) J. Biol. Chem. 258: 9178–9183.

    CAS  Google Scholar 

  49. Evain, D., Binet, E., and Anderson, W.B. (1981) J. Cell. Physiol. 109: 453–459.

    Article  CAS  Google Scholar 

  50. Niles, R.M., and Loewy, B.P. (1989) Cancer Res. 49: 4483–4487.

    CAS  Google Scholar 

  51. Boutwell, R.K. (1974) Crit. Rev. Toxicol. 2: 419–443.

    Article  CAS  Google Scholar 

  52. Verma, A.K., Rice, H.M., Shapas, B.G., and Bontwell, R.R. (1978) Cancer Res. 38: 793–801.

    CAS  Google Scholar 

  53. Paranjpe, M., DeLarco, J., and Todaro, G. (1980) Biochem. Biophys. Res. Commun. 94: 586–591.

    Article  CAS  Google Scholar 

  54. Astrup, E.G., and Paulsen, J.E. (1982) Carcinogenesis 3: 313–320.

    Article  CAS  Google Scholar 

  55. Yuspa, S., Lichti, U., Ben, T., and Hennings, H. (1981) Ann. N.Y. Acad. Sci. 359: 260–273.

    Article  CAS  Google Scholar 

  56. Zerlauth, G., and Wolf, G. (1984) Carcinogenesis 5: 863–868.

    Article  CAS  Google Scholar 

  57. Zerlauth, G., and Wolf, G. (1985) Carcinogenesis 6: 531–534.

    Article  CAS  Google Scholar 

  58. Plet, A., Gerbaud, P., Anderson, W.B., and EvainBrion, D. (1988) Cancer Res. 48: 3993–3997.

    CAS  Google Scholar 

  59. Byus, C.V., Trevillyan, J.M., Cavit, L.J., and Fletcher, W.H. (1983) Cancer Res. 43: 3321–3326.

    CAS  Google Scholar 

  60. Jetten, A., and Shirley, J. (1986) Exp. Cell Res. 166: 519–525.

    Article  CAS  Google Scholar 

  61. Driedger, P.E., and Blumberg, P.M. (1980) Proc. Natl. Acad. Sci. USA 77: 567–571.

    Article  CAS  Google Scholar 

  62. Shoyab, M., and Todaro, G. J. (1980) Nature 288: 45–1458.

    Article  Google Scholar 

  63. Slater, T.F. (1984) Biochem. J. 222: 1–15.

    CAS  Google Scholar 

  64. Halliwell, B., and Gutteridge, J.M.C. (1984) Biochem. J. 219: 1–14.

    CAS  Google Scholar 

  65. Kensler, T.W., and Taffe, B.G. (1986) Adv. Free Radical Biol. Med. 2: 347–387.

    Article  Google Scholar 

  66. Blumberg, P.M., Jaken, S., Konig, B., Sharkey, N.A., Leach, K., Jeng, A.Y., and Yeh, E. (1984) Biochem. Pharmacol. 33: 933–940.

    Article  CAS  Google Scholar 

  67. Slags, T.J., Klein-Szanto, A.J.P., Triplett, L.L., Yotti, L.P., and Trosko, J.E. (1981) Science 273: 1023–1025.

    Article  Google Scholar 

  68. Bull, A.W., Nigio, N.D., and Marnett, L.J. (1988) Cancer Res. 48: 1771–1776.

    CAS  Google Scholar 

  69. Goldstein, B.D., Witz, G., Amoruso, M., Stone, D.S., and Troll, W. (1981) Cancer Lett. 11: 257–262.

    Article  CAS  Google Scholar 

  70. Slaga, T.J., Fischer, S.M., Weeks, C.E., Klein-Szanto, A.J.P., and Reinders, J. (1982) J. Cell. Biochem. 18: 99–119.

    Article  CAS  Google Scholar 

  71. Ames, B.N. (1983) Science 221: 1256–1263.

    Article  CAS  Google Scholar 

  72. Kensler, T., Bush, D.M., and Kazumbo, W.J. (1983) Science 221: 75–77.

    Article  CAS  Google Scholar 

  73. Emerit, I., Levy, A., and Cerutti, P.A. (1983) Mutat. Res. 110: 327–335.

    Article  CAS  Google Scholar 

  74. Friedman, J., and Cerutti, P.A. (1983) Carcinogenesis 4: 1425–1427.

    Article  CAS  Google Scholar 

  75. Gopalakrishna, R., and Anderson, W.G. (1989) Proc. Natl. Acad. Sci. USA 86:in press.

    Google Scholar 

  76. Witz, G., Goldstein, B.D., Amoruso, M., Stone, D.S., and Troll, W. (1980) Biochem. Biophys. Res. Commun. 97: 883–888.

    Article  CAS  Google Scholar 

  77. Kunert, K.J., and Tappel, A.L. (1983) Lipids 18: 271–274.

    Article  CAS  Google Scholar 

  78. Weitberg, A.B., Weitzmann, S.A., Clarke, E.P., and Stossel, T.P. (1985) J. Clin. Invest. 75: 1835–1841.

    Article  CAS  Google Scholar 

  79. Tappel, A.L. (1972) Ann. N.Y. Acad. Sci. 203: 12–27.

    Article  CAS  Google Scholar 

  80. McCay, P.B., and King, M.M. (1980) in Vitamin E (Machlin, L., ed.) pp. 289–317, Dekkar, New York.

    Google Scholar 

  81. Gopalakrishna, R., and Anderson, W.B. (1987) FEBS Lett. 225: 233–237.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular Oncology, NCI, NIH, Bethesda, MD, USA, 20892

    W. B. Anderson, C. Liapi & J. Strasburger

  2. Department of Pathology, UCLA School of Medicine, Los Angeles, CA, USA, 90024

    R. Gopalakrishna

  3. Laboratoire de Physiopathologie du Developpement, CNRS-ENS, 75230, Paris, Cedex 05, France

    A. Plet, F. Raynaud & D. Evain-Brion

Authors
  1. W. B. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Liapi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Strasburger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Gopalakrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Plet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Raynaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. Evain-Brion
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Health Sciences Center, University of Colorado, 4200 East Ninth Avenue, 80262, Denver, CO, USA

    Kedar N. Prasad

  2. Irvine Medical Center, University of California, 101 The City Drive, Building 44, Route 81, 92668-3297, Orange, CA, USA

    Frank L. Meyskens Jr.

Rights and permissions

Reprints and permissions

Copyright information

© 1990 The Humana Press Inc.

About this chapter

Cite this chapter

Anderson, W.B. et al. (1990). Counteractions of Retinoic Acid and Phorbol Ester Tumor Promoter Related to Changes in Protein Kinase Activities. In: Prasad, K.N., Meyskens, F.L. (eds) Nutrients and Cancer Prevention. Experimental Biology and Medicine, vol 23. Humana Press. https://doi.org/10.1007/978-1-4612-4516-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-4516-2_2

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-4612-8856-5

  • Online ISBN: 978-1-4612-4516-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation