Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/2/2007
Publication Date: 3/6/2007
Citation: Su, Y., Simmen, F.A., Xiao, R., Simmen, R.C. 2007. Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors. Physiological Genomics. 30(1):8-16.
Interpretive Summary: The linkage between nutrition and cancer prevention has been widely studied. In our lab, we have shown that lifetime consumption of diets made with soy protein isolate (SPI) is protective in a rat model of human breast cancer. Here we report the effects of various diets on those cell types in the mammary gland where cancers typically develop, the epithelial cells, Young adult female rats that were fed AIN-93G diets made with casein, casein + genistein or soy protein isolate. Genistein is a phytochemical in the protein. Our results suggest that diet can alter the way various genes are turned on or turn off. This now provides us with enough information to conduct future research into how the dietary factors in soy protein actually do this and to identify the specific soy factors that are responsible for the cancer protective effects of soy consumption in early life.
Technical Abstract: The role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and '-catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer.