The Roles of TGF-Beta and TGF-Beta Signaling Receptors in Breast Carcinogenesis.
Annual rept. 1 Jul 95-30 Jun 96,
DUKE UNIV MEDICAL CENTER DURHAM NC
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The overall goal of this research project is to explore the roles of TGF-l3 and components of its signaling pathways in the initiation, progression and metastasis of breast adenocarcinomas through an investigation of the disregulation of TGF-B signal transduction. We have identified and isolated two cDNAs encoding members of the Dwarfins family and studied the TGF-B induced phosphorylation of these two molecules in a normal mammary epithelial cell line. Further studies are underway to address the functional significance of the induced phosphorylation in the mediation of the TGF-B growth inhibitory signal. We have also investigated the importance of a paracrine loop involving the interactions between mammary epithelial and fibroblast cells. We specifically studied the regulation of IGFBP3 expression in the presence of TGF-B. The results indicated that, in addition to its direct effect on the cell cycle progression, TGF-B may have a broader role in affecting the epithelial cell proliferation through its induction of IGFBP3 in fibroblast, consequently blocking the action of mitogenic factors, such as IGF, in breast tissues. Results from further analysis in this action 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.
- Medicine and Medical Research