TGF-Beta and Breast Cancer Induction
Abstract
The breast produces inhibitors of mammary tumor formation. We hypothesized increases in 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 complex consisting of the TGF-beta homodimer, the TGF-beta propeptide dimmer, 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 propetide 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 control of breast specific WAP promoter, and will generate mice overexpressing CR3 under 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, 2001
- Accession Number
- ADA396610
Entities
People
- Branka B. Dabovic
Organizations
- New York University