Human cervical cancer. Retinoids, interferon and human papillomavirus

Adv Exp Med Biol. 1995:375:31-44.

Abstract

Our studies highlight the importance of dietary vitamin A (retinol) and other retinoids in maintaining normal cervical cell function and in inhibiting the growth of cervical tumors. Based on our results we conclude that 1) HPV 16-immortalization enhances cervical cell sensitivity to retinoids, 2) cytokeratin expression may be useful as a marker for evaluating the success of retinoid therapy in vivo, 3) retinoids do not necessarily act to inhibit proliferation of HPV-immortalized cervical cells via effects on HPV E6 and E7 RNA levels and 4) retinoids may act to inhibit cervical proliferation by "suppressing" the activity of the EGF and IGF signalling pathways. Based on these and other results, it is worth considering the possibility that vitamin A or related retinoids could be administered therapeutically, early in the neoplastic process (either systemically or locally), to inhibit the progress of the disease. These results also suggest that combined interferon/retinoid therapy may provide an enhanced beneficial effect to reduce cervical tumor size due to the fact that each agent is inhibiting cervical cell proliferation via distinct, but reinforcing, pathways (i.e., IFN gamma reduces E6/E7 expression, RA inhibits the function of the EGF and IGF1 signalling pathways).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Epidermal Growth Factor / metabolism
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Interferons / physiology*
  • Interferons / therapeutic use
  • Papillomaviridae* / drug effects
  • Papillomaviridae* / genetics
  • Papillomavirus Infections
  • Retinoids / metabolism
  • Retinoids / pharmacology*
  • Retinoids / therapeutic use
  • Signal Transduction
  • Tumor Virus Infections
  • Uterine Cervical Neoplasms* / prevention & control
  • Uterine Cervical Neoplasms* / therapy
  • Uterine Cervical Neoplasms* / virology

Substances

  • Retinoids
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Interferons