Skip to main content
SpringerLink
Log in

Retinoic Acid Suppresses Human Papillomavirus Type 16 (HPV16)-Mediated Transformation of Human Keratinocytes and Inhibits the Expression of the HPV16 Oncogenes

  • Chapter
Diet and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 375))

Abstract

It has been estimated that approximately 35% of cancer deaths occurring now may be related to diet, and that diet may constitute the greatest lifestyle contribution to cancer mortality.1 Of the numerous dietary constituents related to cancer risk, β-carotene and/or vitamin A have consistently been implicated as potential agents for the chemoprevention of cancer in humans.2–7 Vitamin A and its natural and synthetic derivatives (collectively known as retinoids) have been shown to inhibit both chemical8 and viral carcinogenesis.9,10 For example, retinoids inhibit skin carcinogenesis in the classic two-stage system11 and exert a marked inhibitory effect on the induction and development of virus-induced papilloma (Shope) of rabbit skin.9,10 In addition, numerous epidemiological studies have demonstrated an inverse correlation between dietary intake or blood levels of vitamin A and/or its precursors, the carotenoids, and cancer risk at several epithelial sites,12–17 including the cervix.18–21 Retinoids also may be effective in treating premalignant lesions such as cervical intraepithelial neoplasia (CIN).22–27 In fact, phase I and phase II clinical trials of all-trans-retinoic acid (RA) for CIN have shown that RA is capable of reversing cervical dysplasia in some patients, indicating that retinoids may be useful in the prevention and treatment of cervical malignancies.22–27

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. R. Doll, R. Peto, The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today, J Natl Cancer Inst 66:1292 (1981).

    Google Scholar 

  2. J.S. Bertram, L.N. Kolonel, F.L. Meyskens, Rationale and strategies for chemoprevention of cancers in humans, Cancer Res 47:3012 (1987).

    CAS  PubMed  Google Scholar 

  3. R. Peto, R. Doll, J.D. Buckley, M.B. Sporn, Can dietary beta-carotene materially reduce human cancer rates? Nature 290:201 (1981).

    Article  CAS  PubMed  Google Scholar 

  4. R.C. Moon, L.M. Itri, Retinoids and cancer, in: The Retinoids, M.B. Sporn, A.B. Roberts, D.S. Goodman, eds., Vol. 2, p. 327, Academic Press, New York (1984).

    Google Scholar 

  5. G.L. Peck, Chemoprevention of cancer with retinoids, Gynecol Oncol 12:s331 (1981).

    Article  CAS  PubMed  Google Scholar 

  6. D.L. Hill, C.L. Grubbs, Retinoids as chemopreventive and anticancer agents in intact animals (review), Anticancer Res 2:111 (1982).

    CAS  PubMed  Google Scholar 

  7. S.M. Lippman, J.F. Kessler, F.L. Meyskens, Retinoids as preventive and therapeutic anticancer agents (part I), Cancer Treat Rep 71:391 (1987).

    CAS  PubMed  Google Scholar 

  8. M.B. Sporn, N.M. Dunlop, D.L. Newton, Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids), Fed Proc 35:1332 (1976).

    CAS  PubMed  Google Scholar 

  9. Y. Ito, Effect of an aromatic retinoic acid analog (RO 10-9359) on growth of virus-induced papilloma (Shope) and related neoplasia of rabbits, Eur J Cancer 17:35 (1981).

    CAS  PubMed  Google Scholar 

  10. H. McMichael, Inhibition of growth of Shope rabbit papilloma by hypervitaminosis A, Cancer Res 25:947 (1965).

    CAS  PubMed  Google Scholar 

  11. A.K. Verma, B.G. Shapas, H.M. Rice, R.K. Boutwell, Correlation of the inhibition by retinoids of tumor promoter-induced mouse epidermal ornithine decarboxylase activity and of skin tumor promotion, Cancer Res 39:419 (1979).

    CAS  PubMed  Google Scholar 

  12. E. Bjelke, Dietary vitamin A and human lung cancer, Int J Cancer 15:561 (1975).

    Article  CAS  PubMed  Google Scholar 

  13. S. Graham, Results of case-control studies of diet and cancer in Buffalo, New York, Cancer Res 43:2409s (1983).

    CAS  PubMed  Google Scholar 

  14. J.D. Kark, A.H. Smith, B.R. Switzer, C.G. Harnes, Serum vitamin A (retinol) and cancer incidence in Evans County, Georgia, J Natl Cancer Inst 66:7 (1981).

    CAS  PubMed  Google Scholar 

  15. C. Mettlin, S. Graham, M. Swanson, Vitamin A and lung cancer, J Natl Cancer Inst 62:1435 (1979).

    CAS  PubMed  Google Scholar 

  16. R.B. Shekelle, M. Lepper, S. Liu, C. Maliza, WJ. Raynor, A.H. Rossof, O. Paul, A.M. Shyrock, J. Stamler, Dietary vitamin A and risk of cancer in the Western Electric study, Lancet ii: 1185 (1981).

    Article  Google Scholar 

  17. N. Wald, M. Idle, J. Boreham, A. Bailey, Low serum-vitamin-A and subsequent risk of cancer, Lancet ii:813 (1980).

    Article  Google Scholar 

  18. A. Bernstein, B. Harris, The relationship of dietary and serum vitamin A to the occurrence of cervical intraepithelial neoplasia in sexually active women, Am J Obstet Gynecol 148:309 (1984).

    CAS  PubMed  Google Scholar 

  19. T. Hirayama, Diet and cancer, Nutr Cancer 1:67 (1979).

    Article  Google Scholar 

  20. J.R. Marshall, S. Graham, T. Byers, M. Swanson, J. Brasure, Diet and smoking in the epidemiology of cancer of the cervix, J Natl Cancer Inst 70:847 (1983).

    CAS  PubMed  Google Scholar 

  21. S.L. Romney, P.R. Palan, C. Duttagupta, S. Wassertheil-Smoller, J. Wylie, G. Miller, N.S. Slagle, D. Lucido, Retinoids and the prevention of cervical dysplasias, Am J Obstet Gynecol 141:890 (1981).

    CAS  PubMed  Google Scholar 

  22. V. Graham, E.A. Surwit, S. Weiner, F.L. Meyskens, Phase II trial of β-all-trans-retinoic acid for cervical intraepithelial neoplasia delivered via a collagen sponge and cervical cap, West J Med 145:192 (1986).

    CAS  PubMed  Google Scholar 

  23. F.L. Meyskens, V. Graham, M. Chvapil, R.T. Dorr, D.S. Alberts, E.A. Surwit, A phase I trial of β-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia, J Natl Cancer Inst 71:921 (1983).

    PubMed  Google Scholar 

  24. F.L. Meyskens, E.S. Surwit, Clinical experience with topical tretinoin in the treatment of cervical dysplasia, J Am Acad Dermatol 15:826 (1986).

    Article  PubMed  Google Scholar 

  25. Y.M. Peng, D.S. Alberts, V. Graham, E.A. Surwit, S. Weiner, F.L. Meyskens, Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia, Invest New Drugs 4:245 (1986).

    Article  CAS  PubMed  Google Scholar 

  26. E.A. Surwit, V. Graham, W. Droegemueller, D. Alberts, M. Chvapil, R.T. Dorr, J.R. Davis, F.L. Meyskens, Evaluation of topically applied trans-retinoic acid in the treatment of cervical intraepithelial lesions, Am J Obstet Gynecol 143:821 (1982).

    CAS  PubMed  Google Scholar 

  27. S.A. Weiner, E.A. Surwit, V.E. Graham, F.L. Meyskens, A phase I trial of topically applied trans-retinoic acid in cervical dysplasia-clinical efficacy, Invest New Drugs 4:241 (1986).

    Article  CAS  PubMed  Google Scholar 

  28. H. zur Hausen, Papillomaviruses in human cancers, Mol Carcinogenesis 1:147 (1988).

    Article  Google Scholar 

  29. H. zur Hausen, Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers, Cancer Res 49:4611 (1989).

    Google Scholar 

  30. L. Pirisi, S. Yasumoto, M. Feller, J. Doniger, J.A. DiPaolo, Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA, J Virol 61:1061 (1987).

    CAS  PubMed  Google Scholar 

  31. L. Pirisi, K.E. Creek, J. Doniger, J.A. DiPaolo, Continuous cell lines with altered growth and differentiation properties originate after transfection of human keratinocytes with human papillomavirus type 16 DNA, Carcinogenesis 9:1573 (1988).

    Article  CAS  PubMed  Google Scholar 

  32. M. Durst, R.T. Dzarlieva-Petrusevska, P. Boukamp, N.E. Fusenig, L. Gissmann, Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA, Oncogene 1:251 (1987).

    CAS  PubMed  Google Scholar 

  33. C.D. Woodworth, J. Doniger, J.A. DiPaolo, Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma, J Virol 63:159 (1989).

    CAS  PubMed  Google Scholar 

  34. P. Kaur, J.K. McDougall, Characterization of primary human keratinocytes transformed by human papillomavirus type 18, J Virol 62:1917 (1988).

    CAS  PubMed  Google Scholar 

  35. CD. Woodworth, P.E. Bowden, J. Doniger, L. Pirisi, W. Barnes, W.D. Lancaster, J.A. DiPaolo, Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA, Cancer Res 48:4620 (1988).

    CAS  PubMed  Google Scholar 

  36. R. Schlegel, W.C. Phelps, W.L. Zhang, M. Barbosa, Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma, EMBO J 5:3181 (1988).

    Google Scholar 

  37. C.C. Baker, W.C. Phelps, V. Lindgren, M.J. Braun, M.A. Gonda, P.M. Howley, Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines, J Virol 61:962 (1987).

    CAS  PubMed  Google Scholar 

  38. E. Schwarz, U.K. Freese, L. Gissmann, W. Mayer, B. Roggenbuck, A. Stremlau, H. zur Hausen, Structure and transcription of human papillomavirus sequences in cervical carcinoma cells, Nature 314:111 (1985).

    Article  CAS  PubMed  Google Scholar 

  39. C. Yee, I. Krishnan-Hewlett, C.C Baker, R. Schlegel, P.M. Howley, Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines, Am J Pathol 119:361 (1985).

    CAS  PubMed  Google Scholar 

  40. T. Crook, J.P. Morgenstern, L. Crawford, L. Banks, Continued expression of HPV-16 E7 protein is required for maintenance of the transformed phenotype of cells co-transformed by HPV-16 plus EJ-ras, EMBO J 8:513 (1989).

    CAS  PubMed  Google Scholar 

  41. P. Hawley-Nelson, K.H. Vousden, N.L. Hubbert, D.R. Lowy, J.T. Schiller, HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes, EMBO J 8:3905 (1989).

    CAS  PubMed  Google Scholar 

  42. J.B. Hudson, M.A. Bedell, DJ. McCance, L.A. Laimins, Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18, J Virol 64:519 (1990).

    CAS  PubMed  Google Scholar 

  43. M.S. Barbosa, R. Schlegel, The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes, Oncogene 4:1529 (1989).

    CAS  PubMed  Google Scholar 

  44. CL. Halbert, G.W. Demers, D.A. Galloway, The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells, J Virol 65:473 (1991).

    CAS  PubMed  Google Scholar 

  45. W.C Phelps, C.L. Yee, K. Munger, P.M. Howley, The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A, Cell 53:539 (1988).

    Article  CAS  PubMed  Google Scholar 

  46. N. Dyson, P.M. Howley, K. Munger, E. Harlow, The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product, Science 243:934 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. K. Munger, B.A. Werness, N. Dyson, W.C. Phelps, E. Harlow, P.M. Howley, Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product, EMBO J 8:4099 (1989).

    CAS  PubMed  Google Scholar 

  48. J.R. Gage, C. Meyers, F.O. Wettstein, The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding and other properties, J Virol 64:723 (1990).

    CAS  PubMed  Google Scholar 

  49. B.A. Werness, AJ. Levine, P.M. Howley, Association of human papillomavirus types 16 and 18 E6 proteins with p53, Science 248:76 (1990).

    Article  CAS  PubMed  Google Scholar 

  50. K.E. Creek, C.S. Silverman-Jones, L.M. De Luca, Comparison of the uptake and metabolism of retinol delivered to primary mouse keratinocytes either free or bound to rat serum retinol-binding protein, J Invest Dermatol 92:283 (1989).

    Article  CAS  PubMed  Google Scholar 

  51. S. Yasumoto, J. Doniger, J.A. DiPaolo, Differential early viral gene expression in two stages of human papillomavirus type 16 DNA-induced malignant transformation, Mol Cell Biol 7:2165 (1987).

    CAS  PubMed  Google Scholar 

  52. U.K. Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227:680 (1970).

    Article  CAS  PubMed  Google Scholar 

  53. S.D. Dunn, Effects of the modification of transfer buffer composition and renaturation of proteins in gels on the recognition of proteins on western blots by monoclonal antibodies, Anal Biochem 157:144 (1986).

    Article  CAS  PubMed  Google Scholar 

  54. L. Pirisi, A. Batova, G.R. Jenkins, J.R. Hodam, K.E. Creek, Increased sensitivity of human keratinocytes immortalized by human papillomavirus type 16 DNA to growth control by retinoids, Cancer Res 52:187 (1992).

    CAS  PubMed  Google Scholar 

  55. M. Petkovich, N.J. Brand, A. Krust, P. Chambon, A human retinoic acid receptor which belongs to the family of nuclear receptors, Nature 330:444 (1987).

    Article  CAS  PubMed  Google Scholar 

  56. V. Giguere, E.S. Ong, P. Segui, R.M. Evans, Identification of a receptor for the morphogen retinoic acid, Nature 330:624 (1987).

    Article  CAS  PubMed  Google Scholar 

  57. R.M. Evans, The steroid and thyroid hormone receptor superfamily, Science 240:889 (1988).

    Article  CAS  PubMed  Google Scholar 

  58. L.J. Gudas, Retinoids, retinoid-responsive genes, cell differentiation, and cancer, Cell Growth Differentiation 3:655 (1992).

    CAS  PubMed  Google Scholar 

  59. L.M. De Luca, Retinoids and their receptors in differentiation, embryogenesis, and neoplasia, FASEB J 5:2924 (1991).

    PubMed  Google Scholar 

  60. N. Brand, M. Petkovich, A. Krust, P. Chambon, H. de The, A. Marchio, P. Tiollais, A. Dejean, Identification of a second human retinoic acid receptor, Nature 332:850 (1988).

    Article  CAS  PubMed  Google Scholar 

  61. D. Benbrook, E. Lernhardt, M. Pfahl, A new retinoic acid receptor identified from a hepatocellular carcinoma, Nature 333:669 (1988).

    Article  CAS  PubMed  Google Scholar 

  62. A. Krust, P. Kastner, M. Petkovich, A. Zelent, P. Chambon, A third human retinoic acid receptor, hRAR-gamma, Proc Natl Acad Sci USA 86:5310 (1989).

    Article  CAS  PubMed  Google Scholar 

  63. A. Zelent, A. Krust, M. Petkovich, P. Kastner, P. Chambon, Cloning of murine α and β retinoic acid receptors and a novel receptor gamma predominantly expressed in skin, Nature 339:714 (1989).

    Article  CAS  PubMed  Google Scholar 

  64. K. Umesono, V. Giguere, C.K. Glass, M.G. Rosenfeld, R.M. Evans, Retinoic acid and thyroid hormone induce gene expression through a common responsive element, Nature 336:262 (1988).

    Article  CAS  PubMed  Google Scholar 

  65. B. Gloss, H.U. Bernhard, K. Seedorf, G.A. Klock, A DNA segment of the upstream regulatory region of the human papillomavirus-16 exhibits E2 protein-independent enhancer activity in a glucocorticoid hormone-regulated and cell type-specific fashion, EMBO J 6:3735 (1987).

    CAS  PubMed  Google Scholar 

  66. T. Chong, W.K. Chan, H.U. Bernard, Transcriptional activation of human papillomavirus 16 by nuclear factor I, AP1, steroid receptors and a possibly novel transcription factor, PVF: A model for the composition of genital papillomavirus enhancers, Nucleic Acids Res 18:465 (1990).

    Article  CAS  PubMed  Google Scholar 

  67. R.C. Nicholson, S. Mader, S. Nagpal, M. Leid, C. Rochette-Egly, P. Chambon, Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site, EMBO J 9:4443 (1990).

    CAS  PubMed  Google Scholar 

  68. D. Bartsch, B. Boye, C. Baust, H. zur Hausen, E. Schwarz, Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor β gene in non-tumorigenic and tumorigenic HeLa hybrids, EMBO J 11:2283 (1992).

    CAS  PubMed  Google Scholar 

  69. A. Batova, D. Danielpour, L. Pirisi, K.E. Creek, Retinoic acid induces secretion of latent transforming growth factor β1 and β2 in normal and human papillomavirus type 16-immortalized human keratinocytes, Cell Growth Differentiation 3:763 (1992).

    CAS  PubMed  Google Scholar 

  70. A.B. Glick, K.C. Flanders, D. Danielpour, S.H. Yuspa, M.B. Sporn, Retinoic acid induces transforming growth factor-β2 in cultured keratinocytes and mouse epidermis, Cell Regulation 1:87 (1989).

    CAS  PubMed  Google Scholar 

  71. G.D. Shiply, M.R. Pittelkow, J.J. Wille, R.E. Scott, H.L. Moses, Reversible inhibition of normal human prokeratinocyte proliferation by type β transforming growth factor-growth inhibitor in serum-free medium, Cancer Res 46:2068 (1986).

    Google Scholar 

  72. R.J. Coffey, N.J. Sipes, C.C. Bascom, R. Graves-Deal, C.Y. Pennington, B.E. Weissman, H.L. Moses, Growth modulation of mouse keratinocytes by transforming growth factors, Cancer Res 48:1596 (1988).

    CAS  PubMed  Google Scholar 

  73. M. Reiss, A.C. Sartorelli, Regulation of growth and differentiation of human keratinocytes by type β transforming growth factor and epidermal growth factor, Cancer Res 47:6705 (1987).

    CAS  PubMed  Google Scholar 

  74. P.A. Dennis, D.B. Rifkin, Cellular activation of latent transforming growth factor β requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor, Proc Natl Acad Sci USA 88:580 (1991).

    Article  CAS  PubMed  Google Scholar 

  75. C.D. Woodworth, V. Notario, J.A. DiPaolo, Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells, J Virol 64:4767 (1990).

    CAS  PubMed  Google Scholar 

  76. J.A. Pietenpol, R.W. Stein, E. Moran, P. Yaciuk, R. Schlegel, R.M. Lyons, M.R. Pittelkow, K. Munger, P.M. Howley, H.L. Moses, TGF-α1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains, Cell 61:777 (1990).

    Article  CAS  PubMed  Google Scholar 

  77. C. Agarwal, E.A. Rorke, J.C. Irwin, R.L. Eckert, Immortalization by human papillomavirus type 16 alters retinoid regulation of human ectocervical epithelial cell differentiation, Cancer Res 51:3982 (1991).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA

    Kim E. Creek, G. Ronald Jenkins, Ayse Batova & John R. Hodam

  2. Department of Pathology, University of South Carolina School of Medicine, Columbia, SC, 29208, USA

    Mohammad A. Khan, William H. Tolleson & Lucia Pirisi

Authors
  1. Kim E. Creek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Ronald Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad A. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayse Batova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John R. Hodam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William H. Tolleson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lucia Pirisi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. American Institute for Cancer Research, Washington, D.C., USA

    Maryce M. Jacobs

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Creek, K.E. et al. (1994). Retinoic Acid Suppresses Human Papillomavirus Type 16 (HPV16)-Mediated Transformation of Human Keratinocytes and Inhibits the Expression of the HPV16 Oncogenes. In: Jacobs, M.M. (eds) Diet and Cancer. Advances in Experimental Medicine and Biology, vol 375. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0939-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0939-8_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0941-1

  • Online ISBN: 978-1-4899-0939-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation