Accession Number:

ADB264797

Title:

The Effects of IGFBP3 Induction by TFG-B in Breast Tumorigenesis

Descriptive Note:

Final rept. 1 Sep 1997-31 Aug 2000

Corporate Author:

DUKE UNIV MEDICAL CENTER DURHAM NC

Personal Author(s):

Report Date:

2000-09-01

Pagination or Media Count:

87.0

Abstract:

The goal of this research is to study the role of the antagonistic relationship between two opposing growth signals, IGF and TGFbeta, in mammary turmorigenesis. We set out to test a hypothesis that the induction of IGFBP-3 by TGF-beta in stromal fibroblasts is a mechanism by which TGF-beta regulates the growth of breast epithelial cells. To do this, a model cell culture system was established in which the effects of TGF-beta through IGFBP-3 could be studied. Our results show that recombinant IGFBP-3 is able to block IGF-induced growth of breast cancer cells, however the effects of secreted IGFBP-3 from fibroblast media are unclear. Growth inhibition does occur, but the presence of other molecules in this system cloud IGFBP-3s contribution. Additionally, we set out to define the mechanisms by which TGF-beta induces IGFBP-3 in MRC-9 cells. We determined that the gene is regulated by TOP-a at the level of transcription, and not through mRNA stability. Analysis of the promoter -1800 bp for TOP-a regulatory elements, however, showed that TGF-beta did not significantly induce IGFBP-3 promoter activity in MRC-9 fibroblasts. Therefore, the location of the TGF- beta transciptional regulatory elements in the IGFBP-3 gene remain unknown.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE