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

Previous research from this laboratory indicated that 1) The expression of Tropomyosin-l (TMl), a microfilament-associated protein, is abolished form many human breast carcinoma cells, and; 2) That TMl is suppressor of the malignant transformation. These data led to the hypothesis that TMl plays an important role in mammary carcinogenesis. Therefore, we investigated whether TMl could serve as a biomarker of breast cancer, and TMl could function as a suppressor of the malignant growth of breast cancer cells. Our results show that TMl is downregulated in breast tumors (Objective 1). We demonstrated that TMl is a suppressor of the malignant growth phenotype of MDA MB 231 cells, indicating that TMl is a general suppressor of the transformed growth (Objectives 2). To assess the structure- function relationship of tumor suppression by TMl, we constructed chimeric and variant TMl proteins. By employing a variant TMl that contains an aminoterminal extension, we show that the aminoterminal integrity is important for TMl-mediated tumor suppression (Objective 4) The original document contains color images. All DTIC reproductions will be in black and white.