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Human Cervical Cancer

Retinoids, Interferon and Human Papillomavirus

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Diet and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 354))

Abstract

Cervical cancer is the third most common type of cancer in women in the United States and is the leading cause of cancer deaths in women in third world countries (1,2). Although the pathogenesis of the disease is incompletely understood, human papillomavirus (HPV) is present in over 90% of all high grade cervical lesions and is strongly implicated in the process of cancer development. A common feature of these tumors is expression of the E6 and E7 viral reading frames (3,4,5). These viral genes encode factors, E6 and E7, that interact with the p53 and pRB tumor suppressor genes (6,7,8,9,10). E6 promotes the degradation of p53 via a ubiquitin-dependent pathway (10,11) and E7 interferes with pRB function (8,9,10). Expression of E6 and E7 is sufficient for immortalization of cultured epidermal keratinocytes and cultured cervical epithelial cells (12,13,14,15).

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References

  1. P.J. Disaia, and W.T. Creasman, Preinvasive disease of the cervix, in: “Clinical Gynecologic Oncology,” P.J. Disaia, and W.T. Creasman, eds. Mosby Year Book, St Louis (1993) pp. 1–36.

    Google Scholar 

  2. American Cancer Society: Cancer Facts and Figures. American Cancer Society, Atlanta (1992).

    Google Scholar 

  3. T.R. Broker, Structure and genetic expression of papillomaviruses, Obstet. Gynecol. Clin. North. Am., 14: 329 (1987).

    PubMed  CAS  Google Scholar 

  4. H. zur Hausen, Human papillomaviruses and their possible role in squamous cell carcinomas, Curr. Top. Microbiol. Immunol., 78: 1 (1977).

    Article  PubMed  Google Scholar 

  5. L. Gissmann, M. Boshart, M. Durst, H. Ikenberg, D. Wagner, and H. zur Hausen, Presence of human papillomavirus in genital tumors, J. Invest. Dermatol., 83: 26s (1984).

    Google Scholar 

  6. M.S. Lechner, D.H. Mack, A.B. Finkle, T. Crook, K.H. Vousden, and L A Laimins, Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription, EMBO J., 11: 3045 (1992).

    PubMed  CAS  Google Scholar 

  7. V. Band, J.A. De Caprio, L. Delmolino, V. Kulesa, and R. Sager, Loss of p53 protein in human papillomavirus type 16 E6- immortalized human mammary epithelial cells, J. Virol., 65: 6671 (1991).

    PubMed  CAS  Google Scholar 

  8. P.S. Huang, D.R. Patrick, G. Edwards, P.J. Goodhart, H.E. Huber, L. Miles, V.M. Garsky, A. Oliff, and D.C. Heimbrook, Protein domains governing interactions between E2F, the retinoblastoma gene product, and human papillomavirus type 16 E7 protein, Mol. Cell. Biol. 13: 953 (1993).

    PubMed  CAS  Google Scholar 

  9. D.V. Heck, C.L. Yee, P.M. Howley, and K. Munger, Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses, Proc. Natl. Acad. Sci. USA. 89: 4442 (1992).

    Article  PubMed  CAS  Google Scholar 

  10. K. Munger, M. Scheffner, J.M. Huibregtse, and P.M. Howley, Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer. Surv., 12: 197 (1992).

    PubMed  CAS  Google Scholar 

  11. J.M. Huibregtse, M. Scheffner, and P.M. Howley, A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18, EMBO J., 10: 4129 (1991).

    PubMed  CAS  Google Scholar 

  12. P. Hawley-Nelson, K.H. Vousden, N.L. Hubbert, D.R. Lowy, and J.T. Schiller, HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes, EMBO J., 8: 3905 (1989).

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  14. M.S. Barbosa, and 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).

    PubMed  CAS  Google Scholar 

  15. C.D. Woodworth, J. Doniger, and 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).

    PubMed  CAS  Google Scholar 

  16. A.P. Cullen, R. Reid, M. Campion, and A.T. Lorincz, Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm, J. Virol., 65: 606 (1991).

    PubMed  CAS  Google Scholar 

  17. C.M. Chiang, G. Dong, T.R. Broker, and L.T. Chow, Control of human papillomavirus type 11 origin of replication by the E2 family of transcription regulatory proteins, J. Virol., 66: 5224 (1992).

    PubMed  CAS  Google Scholar 

  18. C.M. Chiang, M. Ustav, A. Stenlund, T.F. Ho, T.R. Broker, and L.T. Chow, Viral El and E2 proteins support replication of homologous and heterologous papillomaviral origins, Proc. Natl. Acad. Sci. U S A., 89: 5799 (1992).

    Article  PubMed  CAS  Google Scholar 

  19. H. Romanczuk, and P.M. Howley, Disruption of either the El or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity, Proc. Natl. Acad. Sci. USA., 89: 3159 (1992).

    Article  PubMed  CAS  Google Scholar 

  20. B.C. Sang, and M.S. Barbosa, Increased E6/E7 transcription in HPV 18-immortalized human keratinocytes results from inactivation of E2 and additional cellular events, Virology, 189: 448 (1992).

    Article  PubMed  CAS  Google Scholar 

  21. R. Sousa, N. Dostatni, and M. Yaniv, Control of papillomavirus gene expression, Biochim. Biophys. Acta, 1032: 19 (1990).

    PubMed  CAS  Google Scholar 

  22. S.L. Romnay, P.R. Palan, and C. Duttagupta, S. Wassertheil-Smolter, J. Wylie, G. Miller, N.S. Slagle, and D. Lucido, Retinoids and the prevention of cervical dysplasia, Am. J. Obst. Gyn., 141: 890 (1981).

    Google Scholar 

  23. W.J. Winkelstein, E.J. Shillitoe, R. Brand, and K.K. Johnson, Further comments on cancer of the uterine cervix, smoking, and herpesvirus infection, Am. J. Epidemiol., 119: 1 (1984).

    PubMed  Google Scholar 

  24. H.Y. Ngan, R.J. Collins, K.Y. Wong, A. Cheung, C.F. Lai, and Y.T. Liu, Cervical human papilloma virus infection of women attending social hygiene clinics in Hong Kong, Int. J. Gynaecol. Obstet., 41: 75 (1993).

    Article  PubMed  CAS  Google Scholar 

  25. S.M. Lippman, B.S. Glisson, J.J. Kavanagh, R. Lotan, W.K. Hong, M. Paredes Espinoza, W.N. Hittelman, E.E. Holdener, and I.H. Krakoff, Retinoic acid and interferon combination studies in human cancer, Eur. J. Cancer, 29A Suppl. 5: S9 (1993).

    Google Scholar 

  26. S.M. Lippman, J.J. Kavanagh, M. Paredes Espinoza, F. Delgadillo Madrueno, P. Paredes Casillas, W.K. Hong, G. Massimini, E.E. Holdener, and I.H. Krakoff, 13-cis-retinoic acid plus interferon-alpha 2a in locally advanced squamous cell carcinoma of the cervix, J. Natl. Cancer Inst., 85: 499 (1993).

    Article  PubMed  CAS  Google Scholar 

  27. S.M. Lippman, and W.K. Hong, 13-cis-retinoic acid and cancer chemoprevention, Monogr. Natl. Cancer Inst., 13: 111 (1992).

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  29. C. Agarwal, J.R. Hembree, E.A. Rorke, and R.L. Eckert, Interferon and retinoic acid suppress the growth of human papillomavirus type 16 immortalized cervical epithelial cells, but only interferon suppresses the level of the human papillomavirus transforming oncogenes, Cancer Res., 54: 2108 (1994).

    PubMed  CAS  Google Scholar 

  30. L. Pirisi, A. Batova, G.R. Jenkins, J.R. Hodam, and 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).

    PubMed  CAS  Google Scholar 

  31. G.I. Gorodeski, R.L. Eckert, W.H. Utian, L. Sheean, and E.A. Rorke, Retinoids, sex steroids and glucocorticoids regulate ectocervical cell envelope formation but not the level of the envelope precursor, involucrin, Differentiation 42: 75 (1989).

    Article  PubMed  CAS  Google Scholar 

  32. G.I. Gorodeski, R.L. Eckert, W.H. Utian and E.A. Rorke, Maintenance of in vivo-like keratin expression, sex steroid responsiveness and estrogen receptor expression in cultured human ectocervical epithelial cells, Endocrinology 126: 399 (1990).

    Article  PubMed  CAS  Google Scholar 

  33. G.I. Gorodeski, R.L. Eckert, W.H. Utian, L. Sheean and E.A. Rorke, Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids and retinoids, J. Clin. Endocrinol. Metab. 70: 1624 (1990).

    Article  PubMed  CAS  Google Scholar 

  34. C.K. Choo, E.A. Rorke and R.L. Eckert, Calcium regulates the differentiation of human papillomavirus type 16 immortalized ectocervical epithelial cells, but not the expression of the papillomavirus E6 and E7 oncogenes, Exper. Cell Res. 208: 161 (1993).

    Article  CAS  Google Scholar 

  35. C.K. Choo, E.A. Rorke, and R.L. Eckert, Differentiation-dependent constitutive expression of the human papillomavirus type 16 E6 and E7 oncogenes in CaSki cervical tumor cells, J. Gen. Virol. 75: 1139 (1994).

    Article  PubMed  CAS  Google Scholar 

  36. N. Sizemore, and E.A. Rorke, Retinoid regulation of human ectocervical epithelial cell transglutaminase activity and keratin gene expression, Differentiation 54: 219 (1993).

    Article  PubMed  CAS  Google Scholar 

  37. L. Kasturi, N. Sizemore, R.L. Eckert, K. Martin, and E.A. Rorke, Calcium modulates cornified envelope formation, involucrin content, and transglutaminase activity in cultured human ectocervical epithelial cells, Exp. Cell. Res. 205: 84 (1993).

    Article  PubMed  CAS  Google Scholar 

  38. S. Andreatta-van Leyen, J.R. Hembree, and R.L. Eckert, Regulation of IGF-I binding protein 3 levels by epidermal growth factor and retinoic acid in cervical epithelial cells, J Cell. Physiol. 160: 265 (1994).

    Article  Google Scholar 

  39. J. Hembree, C. Agarwal and R.L. Eckert, Epidermal growth factor suppresses insulin-like growth factor binding protein-3 levels in human papillomavirus type 16-immortalized cervical epithelial cells and thereby potentiates the effects of IGF-I, Cancer Res. 54: 3160 (1994).

    PubMed  CAS  Google Scholar 

  40. N. Sizemore, and E.A. Rorke, Human papillomavirus 16 immortalization of normal human ectocervical epithelial cells alters retinoic acid regulation of cell growth and epidermal growth factor receptor expression, Cancer Res. 53: 4511 (1993).

    PubMed  CAS  Google Scholar 

  41. C.K. Choo, E.A. Rorke, and R.L. Eckert, Human papillomavirus E6 and E7 oncogene expression is not correlated with cell proliferation or c-myc RNA expression in HPV 16-immortalized human cervical epithelial cells treated with retinoids, Cancer Res. (submitted).

    Google Scholar 

  42. R.A. Pattillo, R.O. Hussa, M.T. Story, A.C. Ruckert, M.R. Shalaby, and R.F. Mattingly, Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line, Science 196: 1456 (1977).

    Article  PubMed  CAS  Google Scholar 

  43. B.M. Gilfix, and R.L. Eckert, Coordinate control by vitamin A of keratin gene expression in human keratinocytes, J. Biol. Chem. 260: 14026 (1985).

    PubMed  CAS  Google Scholar 

  44. R.L. Eckert and H. Green, Cloning of cDNAs specifying vitamin A-responsive human keratins, Proc. Natl. Acad. Sci. USA 81: 4321 (1984).

    Article  PubMed  CAS  Google Scholar 

  45. M. Athar, R. Agarwal, Z.Y. Wang, J.R. Lloyd, D.R. Bickers and H. Mukhtar, All-trans-retinoic acid protects against conversion of chemically induced and ultraviolet B radiation induced skin papillomas to carcinomas, Carcinogenesis 12: 2325 (1991).

    Article  PubMed  CAS  Google Scholar 

  46. N. Sizemore, L. Kasturi, G. Gorodeski R.L. Eckert, A.M. Jetten and E.A. Rorke, Retinoids regulate human ectocervical epithelial cell transglutaminase activity and keratin gene expression, Differentiation 54: 219 (1993).

    Article  PubMed  CAS  Google Scholar 

  47. R.L. Eckert, Structure, function, and differentiation of the keratinocyte, Physiol. Rev., 69: 1316 (1989).

    PubMed  CAS  Google Scholar 

  48. W.S. Cohick and D.R. Clemmons, Regulation of insulin-like growth factor binding protein synthesis and secretion in a bovine epithelial cell line, Endocrinology, 129: 1347 (1991).

    Article  PubMed  CAS  Google Scholar 

  49. D.P. DeLeon, B. Bakker, D.M. Wilson, R.L. Hintz, and R.G. Rosenfeld, Demonstration of insulin-like growth factor (IGF-I and -II) receptors and binding proteins in human breast cancer cell lines, Biochem. Biophys. Res. Comun., 152: 398 (1988).

    Article  CAS  Google Scholar 

  50. R.C. Baxter, and J.L. Martin, Binding proteins for insulin-like growth factors: structure, regulation and function, Prog. Growth Factor Res. 1: 49 (1989).

    Article  PubMed  CAS  Google Scholar 

  51. N. Darwiche, G. Celli, L. Sly, F. Lancillotti, and L.M. De Luca, Retinoid status controls the appearance of reserve cells and keratin expression in mouse cervical epithelium, Cancer Res., 53: 2287 (1993).

    PubMed  CAS  Google Scholar 

  52. R. Moll, W.W. Franke, D.L. Schiller, B. Geiger, and R. Krepler, The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells, Cell 31: 11 (1982).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Physiology and Biophysics, Dermatology, Reproductive Biology, Biochemistry, and Environmental Health Sciences, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio, 44106-4970, USA

    Richard L. Eckert Ph.D., Chapla Agarwal, Joan R. Hembree, Chee K. Choo, Nywana Sizemore, Sheila Andreatta van Leyen & Ellen A. Rorke

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  1. Richard L. Eckert Ph.D.
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  2. Chapla Agarwal
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    © 1995 Springer Science+Business Media New York

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    Eckert, R.L. et al. (1995). Human Cervical Cancer. In: Diet and Cancer. Advances in Experimental Medicine and Biology, vol 354. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0949-7_3

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    • DOI: https://doi.org/10.1007/978-1-4899-0949-7_3

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