Accession Number:

ADA364148

Title:

The Effects of IGFBP-3 Induction by TGF-B in Breast Tumorigenesis

Descriptive Note:

Annual rept. 1 Sep 97-31 Aug 98

Corporate Author:

DUKE UNIV DURHAM NC

Personal Author(s):

Report Date:

1998-09-01

Pagination or Media Count:

11.0

Abstract:

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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE