Evaluation Of Mena Isoforms As A Surrogate For Epithelial Mesenchymal Transformation And Erlotinib Resistance In Breast Carcinoma

1078 Background: Epithelial to mesenchymal transition (EMT) is an important step in invasiveness and has been shown to correlate with metastatic potential in several cancer cell lines, including breast carcinoma. However, given the heterogeneity of tumors in vivo, EMT has not been a reliable marker of metastatic potential in cancer patients. Mena, a member of the enabled (ena)/vasodilator-stimulated phophoprotein (VASP) family, which controls cell motility, is upregulated in the invasive subpopulation of breast cancer cells. Mena is alternatively spliced to include one of four exons: +, ++, invasive (INV), or 11a. In the presence of MenaINV, tumor cells are able to invade even at epidermal growth factor (EGF) concentrations that would otherwise be undetectable by the tumor cells. Currently, there are several clinical and genetic characteristics which can predict sensitivity to erlotinib, an EGF receptor inhibitor, but further studies are necessary. Methods: The animal models used were the polyoma middle T antigen (PyMT) transgenic mouse and severe combined immunodeficiency (SCID) xenografted tumors derived from injection with a human breast carcinoma line, MDA-MB-231, and a rat adenocarcinoma line, MTLn3, with forced expression of MenaINV and Mena11a. Invasive cells and average primary tumor cells were collected using the in vivo invasion assay and Fluorescence activated cell sorting (FACS), respectively, and imaged via immunofluorescence. Results: We show that in both the PyMT and MDA-MB-231 animal models, invasive cells are significantly more mesenchymal than average primary tumor cells, indicating they have undergone EMT. The MTLn3-MenaINV cells are more mesenchymal-like, whereas the Mena11a are more epithelial-like. We also expect that cells with a high Mena INV/11a ratio invade despite the presence of erlotinib. No significant financial relationships to disclose.