The Effects of IGFBP3 Induction by TFG-B in Breast Tumorigenesis
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-3's 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADB264797
Entities
People
- Anita J. Borton
- Xiao-Fan Wang
Organizations
- Duke University Hospital