Estrogens and Breast Cancer
Abstract
In the present work we demonstrate that estradiol and its metabolites mainly 4-OH estradiol are able to induce transformation phenotypes in the human breast epithelial cells (HBEC) MCF-1OF. MCF1OF cells is ER-alpha negative, although, they ER-beta positive that could indicate that the response of the cells to growth and form colonies in agar methocel could be mediated by this receptor. However, the Invasion phenotype is not modified when the cells are treated in presence of tamoxifen or ICI, suggesting that other pathways may be involved. With the data presently available the direct effect of 4-OH-E2 support the concept that metabolic activation of estrogens mediated by various cytochrome P45O complexes, generating through this pathway reactive intermediates that elicit direct genotoxic effects leading to transformation. This assumption was confirmed when we found that all the transformation phenotypes induced by 4-OH-E2 were not abrogated when this compound was used in presence of the pure antiestrogenic ICI. We have detected loss of heterozygosity (LOH) in ch13q12.2-12.3 (D13S893) and in ch17q21.1 that has been reported in primary breast cancer, that the changes are similar to those induced by the chemical carcinogen (BP) and that the genomic changes were not abrogated by antiestrogens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418573
Entities
People
- Jose Russo
Organizations
- Fox Chase Cancer Center