LB-260

Cell migration and adhesion play a central role in many biological and pathological processes, including embryogenesis, the inflammatory response, tissue repair and cancer. Cell surface receptors for the extracellular matrix (ECM), such as integrins, are key regulators of normal and tumor cell migration and survival. Migration leads to invasion, where cells undergo dramatic alterations in integrin expression and binding to ECM components. Estrogen receptor beta (ERβ) is expressed in both normal and malignant breast tissue, and has been shown to inhibit proliferation and invasion of breast cancer cells. The aim of this study was to characterize differences in substrate adhesion and integrin expression induced by ERβ. We used the human breast cancer cell line T47-D, where ERβ expression was induced using a doxycycline-regulated system (T47-DERβ). Cells were seeded on 96-well plates, coated with different matrix proteins, in the presence or absence of doxycycline. Increased adhesion to laminin, primarily, but also collagen type I, collagen type IV, fibronectin, and vitronectin matrix proteins was observed in response to ERβ expression. Characterization of surface integrin expression was evaluated by plating T47-DERβ cells on 96-well plates coated with mouse monoclonal antibodies generated against human alpha and beta integrin subunits. An increase in expression of certain integrin subunits was seen in response to ERβ expression, which was confirmed with FACS. The cells also had a decrease in migratory potential when expressing ERβ, as analyzed with a wound assay. These results suggest that in T47-D breast cancer cells, expression of ERβ results in changes in surface integrin content, which correlates with increased adhesion to ECM substrates and reduced migration. We conclude that ERβ may have a positive role protecting from cancer progression, by increasing adhesion. This in turn affects the migratory properties of cancerous cells, thereby preventing metastasis.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA