Roles of TGF-Beta and TGF-Beta Signaling Receptors in Breast Carcinogenesis

摘要

The overall goal of this research project is to explore the roles of TGF-beta andcomponents of its signaling pathways in the initiation, progression and metastasis of breast adenocarcinomas through an investigation of the disregulation of TGF-beta signal transduction. Last year, we identified and isolated three cDNAs encoding members of the Smad family and studied the TGF-beta induced phosphorylation of these molecules in a normal mammary epithelial cell line. Subsequently, we have focused on the functional role of Smad3 and Smad4 as tumor suppressors in mediating the TGF-beta signal in transactivating downstream target genes. We have also continued our investigation on the mechanism by which TGF-beta activates the expression of cyclin-dependent kinase inhibitor p15 gene in MCF7 cells as well as the importance of a paracrine loop mediated by the interactions between mammary epithelial and fibroblst cells. Results from further analysis in these directions will not only significantly contribute to an understanding of the molecular events leading to breast carcinogenesis, but also aid in the development of new therapeutics for breast cancer.