Functional Analysis of SMAD Activation in TGF-B-mediated Negative Growth Control in Breast Epithlial Cells
Abstract
Transforming growth factor-beta (TGF-beta) is a potent growth inhibitory polypeptide hormone. Although the loss of this negative proliferative signal is often seen in the deregulated growth of early cancer formation, the TGF-beta mediated intracellular pathways that control cell growth remain largely unknown We propose three aims to 1) elucidate the functional role of Smads in TGF-beta signaling, 2) assess their contribution in regulating cell proliferation and 3) to provide evidence that Smad3 acts in vivo as tumor suppressor of early breast cancer formation. In this first year of funding, we have provide evidence that the Smads are specific sequence DNA-binding proteins, and functionally interact wit other transcription factors and the p300/CBP coactivator family of proteins to coordinate disparate pathways in the regulation of specific genes. Towards the goal of the second aim, we have first demonstrated that Smad3 is an essential component of TGF-beta mediated growth inhibition in fibroblast and epithelial cells. The last aim of providing evidence that Smad3 can act as an in vivo breast tumor suppressor will be completed with the use of the Smad3 null mouse model, carcinogen treatment and crossing into other geneticall defined mouse models that are predisosed to breast cancer formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA384127
Entities
People
- Joshua P. Frederick
Organizations
- Duke University Hospital