ESTROGEN METABOLISM AND THE MALIGNANT POTENTIAL OF HUMAN-PAPILLOMAVIRUS IMMORTALIZED KERATINOCYTES

Increased 16 alpha-hydroxylation of estradiol has been shown to be ass ociated with heightened cancer risk in estrogen responsive tissue. Cer tain types of human papillomavirus (HPV) are cofactors for cancer in t he cervix, an estrogen sensitive tissue, We have demonstrated that est radiol and 16 alpha-hydroxyestrone increased the number of cells posit ive for proliferating cell nuclear antigen in HPV immortalized keratin ocytes, the in vitro correlate of the premalignant keratinocyte, These estrogens caused the abnormal proliferation and anchorage independent growth, which correlates with malignant conversion, Indole-3-carbinol , a phytochemical in cruciferous vegetables known to preferentially in duce 2-hydroxylation with minimal effect on 16 alpha-hydroxylation, ma rkedly blocked the ability of estradiol to increase anchorage independ ent growth. The results indicate that 16 alpha-hydroxyestrone increase s the malignant phenotype of HPV immortalized keratinocytes. However, indole-3-carbinol will block this response.