Adipose Estrogen and Increased Breast Cancer Risk in Obesity: Regulation by Leptin and Insulin
Final rept. 15 Aug 2005-7 Sep 2007
LA JOLLA INST FOR MOLECULAR MEDICINE SAN DIEGO CA
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Clinical studies suggest that obesity increases the risk for breast cancer and there is convincing evidence that post-menopausal breast cancer risk is highly correlated with serum estrogen levels. One potential link between obesity and breast cancer risk is increased estrogen production by the adipose tissue itself. Adipose tissue produces the enzyme aromatase, which catalyses the biosynthesis of estrogens from androgens. Adipose tissue also produces 17-beta-hydroxysteroid dehydrogenase 17-beta HSD, which is important for the conversion of estrone to estradiol. Thus, the increased expression of both of these enzymes is important for the production of biologically active estrogen. The investigators studies have identified two key molecules insulin and leptin in obesity that regulate aromatase and 17-beta HSD synthesis in adipose tissues and in adipocytes. The identification of these target molecules that may ultimately induce estrogen production in the setting of obesity may provide a unique therapeutic preventive strategy to reduce systemic estrogen levels and thereby reduce post-menopausal breast cancer risk associated with obesity.
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