Estrogens and Breast Cancer
Abstract
In the present work we have capitalized on the availability in our laboratory of an in vitro model of transformation of immortalized HBEC by the chemical carcinogen BP for comparison with phenotypic and genomic changes induced by the natural estrogen 17b-estradiol (E2). Short term treatment of these cells with physiological doses of 17-b estradiol induces anchorage independent growth, colony formation in agar methocel, and reduced ductulogenic capacity in collagen gel, all phenotypes whose expression is indicative of neoplastic transformation, and that are induce by BP under the same culture conditions. The fact that the MCFlOF cells are both ER-a and ERb. negative, argue in favor of a metabolic activation of estrogens mediated by various cytochrome P450 (CYP) complexes, generating through this pathway reactive intermediates that elicit direct genotoxic effects by increasing mutation rates. We have found that estrogen induces LOll in chromosome 11, as detected using the markers Dl 1S29 and Dl 15912 mapped to 1 1q23.3 and 1 1q24.2-25, respectively. It has been reported that both arms of chromosome 11 contain several regions of LOH in cancers of the breast and of other organs, and that transfer of chromosome 11 to mammary cell lines suppresses tumorigenicity in athymic mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396371
Entities
People
- Jose Russo
Organizations
- Fox Chase Cancer Center