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

The overall goal of this research project is to explore the roles of TGF-B and its signaling receptors in the initiation, progression and metastasis of breast adenocarcinomas through an investigation of the disregulation of TGF-B signal transduction. We have investigated the importance of the type II TGF-B receptor RII in mediating the growth-inhibitory effect of TGF- B in MCF-7 breast carcinoma cells through reconstituting an autocrine system of TGF-B by the re-expression of RII in those cells. The results indicated that the loss of RII consists of a key step in breast carcinogenesis and restoration of the pathway could potentially reverse the tumorigenic phenotype of breast cancer cells. In addition, work is in progress to determine if two inhibitors of the cyclin-dependent kinases, p15 and p21, serve as effectors of the TGF-B growth-inhibitory pathway in breast epithelial cells and whether estrogen could have an effect on this pathway. Results from further analysis in this direction will not only significantly contribute to an understanding of the molecular events leading to breast earcinogenesis, but also aid in the development of new therapeutics for breast cancer.