The Effects of IGFBP-3 Induction by TGF-B in Breast Tumorigenesis
Annual rept. 1 Sep 97-31 Aug 98
DUKE UNIV DURHAM NC
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Transforming growth factor Beta TGF-Beta is a potent growth inhibitor of normal breast epithelia. Evidence is accumulating that TGF-Beta activity is critical to maintaining the negative paracrine and autocrine regulation of breast epithelial growth. Therefore, defects in the TGF-Beta signaling pathways may result in uncontrolled growth of mammary epithelial cells and consequently contribute to carcinogenesis of the breast. TGF-B acts through a direct mechanism as an inhibitor of proliferation in normal breast epithelium by inducing the expression of the cyclinckd inhibitors in several different cell types. Available evidence suggests that TGF-Beta is also able to indirectly mediate its growth inhibitory effects on breast epithelia by inducing the secretion of insulin-like growth factor binding protein 3 IGFBP-3. IGFBPs are a family of molecules which sequester and prevent insulin-like growth factors IGFs from binding and transducing mitogenic signals through the IGF receptors. Our goal is to dissect and elucidate the roles IGF, IGFBP-3, and TGF- Beta in breast tumorigenesis.
- Medicine and Medical Research