TGF-B and Breast Cancer Induction
Abstract
The breast produces inhibitors of breast tumor formation. We hypothesized increases the amount of these compounds would delay cancer onset. We study the molecule TGF- Beta which blocks cell growth. TGF-Beta is produced as latent TGF-Beta complex consisting of the TGF-Beta homodimer, the TGF-Beta propeptide dimer, and a second gene product, the latent TGF-Beta binding protein (LTBP). LTBP targets latent TGF-Beta to the extracellular matrix, from which active TGF-Beta is released. The third cysteine rich repeat (CR3) of LTBP- 1 is necessary and sufficient for covalent interaction with small latent TGF-Beta. CR3 overexpression should result in the TGF-Beta propeptide complexing to an LTBP form unable to interact with matrix. Therefore, TGF-Beta in this complex should be more easily activated. We generated mice overexpressing CR3 under the control of breast specific WAP promotor, and will generate mice overexpressing CR3 under the control of MMTV LTR. We will study whether breast cancer occurrence is delayed compared to wt animals. We will test whether tamoxifen treatment, which prevents breast cancer, and overproduction of TGF Beta in genetically engineered mice block tumorigenesis better than either condition alone.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385519
Entities
People
- Branka B. Dabovic
Organizations
- New York University