Genistein Programming Against Breast Cancer
Abstract
Most soy-breast cancer epidemiological studies conclude that Asian women consuming a traditional diet high in soy products have a low incidence of breast cancer. We have previously demonstrated that prepubertal exposure to genistein, the primary isoflavone of soy, protects against chemically-induced mammary cancer. The purpose of this work was to determine if adult exposure to genistein will protect against chemically-induced mammary cancer and to investigate DNA methylation of estrogen receptor genes as the molecular mechanism of genistein chemoprevention. We have determined that adult only exposure to genistein does not protect against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer. However, prepubertal plus adult exposure to 250 mg genistein/kg AIN-76A diet protected against DMBA-induced mammary cancer. Prepubertal genistein exposure appears to "imprint" for additional adult genistein chemoprevention. Genistein down-regulates ER- alpha, but not ER-beta and androgen receptor, mRNA and protein expression in the rat mammary gland. The down-regulation of ER-alpha is not via DNA methylation gene silencing mechanism as measured via methylation sensitive and insensitive enzymes and Southern blots. On the other hand, genistein in the diet does up regulate overall maintenance, but not de novo, DNA methyltransferase activity, whose specificity needs to be resolved.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA421775
Entities
People
- Coral A. Lamartiniers
Organizations
- University of Alabama