Tropomyosin-1: A Putative Tumor Suppressor and a Biomarker of Human Breast Cancer

Changes in the expression of microfilament-associated proteins such as tropomyosins, are associated with the transformed phenotype. Our previous work demonstrated 1. a complete loss of expression of tropomyosin-1 TM 1 in human breast carcinoma cell lines, indicating that it is a pivotal early event during the neoplastic transformation of mammary epithelium, and 2. TM l is a suppressor of the malignant phenotype. In this work we have tested the hypothesis that TM 1 is putative biomarker and tumor suppressor of breast cancer. To facilitate the analysis of tumor specimens, we developed novel TM 1-specific antibodies. These antibodies are currently being tested in immunohistochemical screening of breast tumors. Restoration of TM 1 expression in MCF-7 MCF-7T cells resulted in slower growth rate and expression of markers associated with normal differentiation status. MCF-7T cells remain sensitive to growth control by estrogen, and TM l re-expression appears to alter the interaction of E-cadherin-catenin complex with microfilaments. More significantly, MCF-7T cells failed to grow under anchorage-independent conditions. Thus, TM 1 appears to be essential for normal growth and differentiation of mammary epithelium. Abolition of TM 1 expression appears to be necessary for malignant transformation by multiple oncogenic modalities. Together, our findings demonstrate that TM 1 is a class II tumor suppressor.