The interaction between HPV infection and estrogen metabolism in cervical carcinogenesis.
Cancer of the genital tract is the final outcome of some infections with human papillomavirus (HPVs), and the most estrogen-sensitive cells are at greatest risk for the HPV-related cancers. Therefore we investigated relationships between HPVs and estrogen metabolism in cells of the genital tract. Increased conversion of estradiol to 16 alpha-hydroxyestrone, known to be a risk factor for cancer in some other estrogen-sensitive cells, was investigated in keratinocytes from the genital tract. Primary cells, particularly those explants from the transformation zone of the cervix, are able to 16 alpha-hydroxylate estradiol. Both cervical and foreskin cells immortalized with HPV-16 are greatly enhanced in the 16 alpha-hydroxylation of estradiol as compared with normal cells. We suggest a model whereby the combined action of 16 alpha-hydroxylation of estrogen and HPV work together to promote cell proliferation.
Auborn
K J
KJ
Department of Otolaryngology, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Woodworth
C
C
DiPaolo
J A
JA
Bradlow
H L
HL
D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D027383:Papillomaviridae / Q000235:genetics; D039181:Steroid 16-alpha-Hydroxylase; D014412:Tumor Virus Infections / Q000150:complications*; D002583:Uterine Cervical Neoplasms / Q000209:etiology*
D004967:Estrogens; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase