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

摘要

Previous research from this laboratory indicated that 1) the expression of Tropomyosin-1 (TM1), a microfilament associated protein, is abolished from many human breast carcinoma cells, and; 2) that TM1 is an anti- oncogene. These data led to the hypothesis that TM1 plays an important role in mammary carcinogenesis. Our results show that TM1 is downregulated in breast tumors (Objective 1). We demonstrated that TM1 is a suppressor of the malignant growth phenotype of MDA MB 231 cells, indicating that TM1 is a general suppressor of the transformed growth by inducing anoikis (Objective 2). We have designed siRNAs to inhibit TM1 expression (Objective 3). To assess the structure-function relationship of tumor suppression by TM1, we constructed chimeric and variant TM1 proteins. By employing a variant TM1 that contains an amino terminal extension, we show that the amino terminal integrity is important for TM1-mediated tumor suppression (Objective 4). Our work illustrates the critical role of TM1 in maintaining normal growth of breast epithelial cells. Future work is directed at elucidating the mechanism of TM1- mediated suppression of breast cancer and determining whether TM1 would be a useful biomarker.