Genotoxicity of steroidal estrogens.
The molecular mechanisms underlying the development of breast cancer in general, and estrogen-associated breast carcinogenesis in particular, are not completely understood. There are three mechanisms considered responsible for the carcinogenicity of estrogens in the human breast: (i) receptor-mediated hormonal activity, which stimulates cellular proliferation, resulting in more opportunities for accumulation of the genetic damage that leads to carcinogenesis; (ii) a cytochrome P450-mediated metabolic activation, which elicits direct genotoxic effects by increasing mutation rates; and (iii) the induction of aneuploidy by estrogen. In this article, we concentrate on discussing the role of estrogen receptors and the metabolic activation of 17beta-estradiol (E(2)) as mechanisms of breast cancer initiation.
Russo
Jose
J
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. J_russo@fccc.edu
Russo
Irma H
IH
D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology*
D011960:Receptors, Estrogen; D004958:Estradiol