TGF-B Regulation of the Mammary Radiation Response
Abstract
Transforming growth factor beta 1 (TGF-beta 1) orchestrates the response of different cell types to injury via regulation of proliferation, apoptosis and ECM composition. Previously we discovered that TGF beta 1 is rapidly activated in mammary gland following radiation. Because TGF- beta 1 is implicated in regulation of proliferation and apoptosis, we investigated whether the activation of TGF-beta 1 contributes to the cell fate decisions in response to radiation. We found that radiation-induced apoptosis and cycle cell arrest are absent in adult mammary epithelium and embryonic liver and epidermis when TGF-beta 1 is compromised. Since p53 abundance and activity is thought to dictate apoptotic cellular responses to radiation, we examined the p53 response. We found that both chronic and transient depletion of TGF-beta 1 compromise the p53 response. In order to study the mechanism by which TGF-beta 1 affects the p53 response we cultured mammary epithelial cells (MECs). This in vitro model present TGF-beta 1 dependent radiation response similar to that seen in vivo. Treatment of MECs with TGF-beta 1 restored both p53 response and caspase 3 cleavage in the heterozygote cultures. We propose that TGF-beta 1 is a key regulator of epithelial genomic integrity since its loss impairs activation of p53 resulting in reduced apoptosis and cell cycle arrest.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA425786
Entities
People
- Maria J. Pajares
Organizations
- University of California, Berkeley