Diet, Stem Cells, and Breast Cancer Prevention
Final rept. 1 Sep 2008-31 Dec 2010
ARKANSAS CHILDREN'S HOSPITAL LITTLE ROCK AR
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Breast cancer is the most common malignancy of women in the Western world. Many risk factors are associated with the development and progression of breast cancer however, dietnutrition constitutes a highly modifiable risk. Breast cancer is considered to be initiated by mutations in a limited population of undifferentiated cells termed mammary stem cells MaSCs sitting at the top of the mammary epithelial hierarchy. Over-expansion of the stem cell population leads to increased numbers of mutated MaSCs that initiate and maintain tumors that can metastasize. Novel strategies to decrease the over-expansion and promote the elimination of tumor-initiating cells are warranted for effective prevention and treatment of breast cancer. Our studies test the hypothesis that dietary factors confer protection from breast cancer by preventing the expansion of MaSCs with tumorigenic potential. We established female mice transgenic for the oncogene Wnt-1 Wnt-Tg mice, which develop spontaneous mammary tumors by 5-6 months of age, as a model for dietary prevention of mammary tumor formation. Mice were fed AIN-93G based isocaloric diets that differed only by protein source, namely control Casein CAS and Soy Protein Isolate SPI. SPI was used as paradigm for healthy foods. We found that lifetime dietary exposure to SPI beginning at post-weaning lowered tumor incidence in Wnt-Tg mice 48.3 relative to those fed the control diet 73.5 P 0.05. Importantly, SPIfed Tg mice had undetectable tumorigenic MaSC population and lower numbers of normal MaSCs, relative to CAS-fed Tg mice at postnatal day 75. Our studies established a functional connection between diet and abundance of MaSCs for breast cancer prevention.
- Medicine and Medical Research