ARS | Publication request: Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: December 15, 2011
Publication Date: April 1, 2012
Citation: Montales, M.E., Scanlon, S., Nakatani, H., Matsuda, T., Simmen, R.C. 2012. Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling. The Federaton of American Societies for Experimental Biology Journal. 26 (Meeting Abstracts):251.1.

Interpretive Summary: Obesity is one of the major concerns in the United States and even worldwide. In this study we are trying to determine the direct relationship between obesity and the occurrence of breast cancer. We are also looking on the effect of diet particularly genistein from soy in inhibiting mammary fat formation (a process which is presumably involve in the proliferation of cancer cells). The method involves cell culture of mammary stromal fibroblast cells (these cells have the ability to convert to fat cells) with and without treatment of genistein. Diet may protect against breast cancer formation through inhibition of fat cell formation.

Technical Abstract: Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mouse mammary stromal fibroblast like cells (MSF) treated with differentiating agents insulin, hydrocortisone and troglitazone (DM). MSF cultured in DM with and without extracellular matrix for 14 days showed reduced differentiation (2-3 fold) into mature adipocytes with 40nM but not 2uM GEN, as evaluated by Oil Red O staining. Addition of sera from GEN-fed adult mice to MSF similarly reduced adipogenic differentiation (4-5 fold), relative to sera from casein-fed mice. Lipid accumulation was decreased by GEN (40nM>2uM). Expression levels of lipogenic enzyme genes fatty acid synthase and PPAR-gamma were down-regulated by 40nM GEN. Estrogen receptor (ER)-beta, an inhibitor of PPAR-gamma transcriptional activity, but not ER-alpha transcript levels were increased by 40 nM GEN. Conditioned media from GEN-treated MSF reduced anchorage-independent mammosphere formation of human breast cancer cells MCF-7. Thus, dietary factor control of mammary adiposity, possibly mediated by ER-beta, may limit mammary stem/progenitor cell expansion and protect against breast cancer.