Accession Number : ADA300368
Title : Initiation of Breast Cancer by Endogenous Estrogens: Mechanism and Prevention.
Descriptive Note : Annual rept. 1 Aug 94-30 Jul 95,
Corporate Author : CORNELL UNIV MEDICAL COLL NEW YORK
Personal Author(s) : Fishman, Jack
PDF Url : ADA300368
Report Date : 30 JUL 1995
Pagination or Media Count : 39
Abstract : We have carried out experiments in cell culture systems demonstrating the unique ability of 16a-OHE1 to bring about hyperproliferation with increased anchorage-independent growth. This, as well as other studies, has indicated the carcinogen like activity of 16a-OHE1. We have also carried out studies with mouse and human explant cultures of two types (high and low risk for breast cancer) and a marked increase in 16a-hydroxylation was observed with cultures from the high risk mice or women. The differences demonstrated in these normal tissues indicate the importance of a chronic increase in estrogen 16a-hydroxylation prior to the development of breast tumors. Experiments with 16a-OHE1 in the control of PS2 gene expression in MCF-7 cells demonstrate that an 'irreversible' interaction between estrogen receptors and 16a-OHE1 can cause sustained response in estrogen-responsive genes. Also, experiments to identity the cytochrome P450 gene which catalyzes estrogen 16a-hydroxylation have indicated that it is probably Cyp2-dx. Further studies should confirm whether or not it is this gene which is responsible for the enzyme. Once identified it may be possible to alter the expression of this gene in breast cells and therefore reduce the risk of breast cancer.
Descriptors : *CARCINOGENS, *MAMMARY GLANDS, *ESTROGENS, *BREAST CANCER, TISSUES(BIOLOGY), HIGH RATE, RISK, ENZYMES, NEOPLASMS, CELLS(BIOLOGY), WOMEN, CULTURES(BIOLOGY), NORMALITY.
Subject Categories : Biology
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE