University of Texas Health Science Center San Antonio United States
A number of recent studies including form our group have shown that exogenous ERBeta expression or its inductionactivation by ERBeta agonists result in blocking the growth of ERalpha-positive breast cancer cells. The central hypothesis of this study is that ERBeta activation andor its overexpression shifts the balance from oncogenic functions of ERalpha to tumor-suppressing actions of ERBeta, thus preventing initiation and progression of breast cancer. In addition, ERBeta activation andor its overexpression prevent and or delay the development of resistance and restores hormonal sensitivity resistant tumors. This study is focused on testing the therapeutic efficacy of ERBeta agonists in preventing and as well as treating and blocking the progression of breast cancers. Significant findings during first year funding period are a Using transgenic animal model we have shown both LY500307 and S-Equol reduced mammary growth and initiation of malignant changes bthis is the first study to investigate the role of ERBeta in the context of breast cancer prevention c ERBeta agonists were able to restore sensitivity to endocrine therapy resistant cells to hormonal therapy and d we have identified novel signaling molecules associated with ERBeta agonists mediated protection.