Abstract 3416: Ubiquitous Brms1 expression is critical for mammary carcinoma metastasis suppression via promotion of apoptosis

Abstract

Morbidity and mortality in breast cancer patients are drastically increased when primary tumor cells are able to spread to distant sites and proliferate to become secondary lesions. Effective treatment of metastatic disease has been limited; therefore, increased molecular understanding to identify biomarkers and targets is needed. We have previously shown that breast cancer metastasis suppressor 1 (Brms1) can suppress development of pulmonary metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Our lab has developed two transgenic Brms1 mouse models, one which expresses murine Brms1 cDNA specifically in mammary tissue (expression by the mouse mammary tumor virus (MMTV) promoter) and a ubiquitous Brms1 expression model (expression by the chicken beta actin promoter). The goal of this study was to investigate mechanisms of Brms1-mediated metastasis suppression in transgenic mice that express Brms1 using a polyoma middle T (PyMT) oncogene-induced model. Brms1 expression, either ubiquitously or predominantly in the mammary gland, did not significantly alter growth of the primary tumor, confirming earlier studies. When expressed ubiquitously, Brms1 suppressed pulmonary metastasis and promoted tumor cell apoptosis in the lung but not in the mammary gland. However, selective expression of Brms1 in the mammary gland using the MMTV promoter did not significantly block metastasis nor did it promote apoptosis in mammary glands or lungs despite increased expression within primary tumors and the lungs. These results suggest tissue- or cell-type specific expression of Brms1 is a critical determinant for Brms1-mediated metastasis suppression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3416. doi:1538-7445.AM2012-3416