Fibroblast TGF-beta Signaling in Breast Development and Cancer
Abstract
Hypothesis: This proposal will address the hypothesis that TGFbeta signals in fibroblasts allow normal mammary gland development; and prevents breast cancer growth and progression. Specific Aims: We will (1) determine the effect of loss of TGFbeta signaling within stromal cells on mammary gland development and (2) determine the effect of loss of TGFbeta signaling within stromal cells on mammary carcinoma development. Study Design: This will be accomplished using transgenic mice with an inducible deletion of the type II TGFbeta receptor (TGFBRII), which is required for TGFbeta? signaling. Cre recombinase driven by Fibroblast-Specific Protein (FSP1) and Pro-Collagen Ialpha2 will delete TGFBRII within fibroblasts. To understand the normal biology of fibroblast TGFbeta signaling, we will first examine mammary gland development in floxed TGFBRII, inducible fibroblast specific-Cre mice. Then we will examine carcinogenesis and tumor progression in floxed TGFBRII, inducible fibroblast-specific Cre, MMTV-PyVmT mice. This is the first proposed model to examine the biology of TGFbeta signaling in fibroblasts in the intact mammary gland. Since TGFbeta can promote or suppress cancer, understanding the roles of fibroblast TGFbeta signaling in breast cancer will allow us to identify patients for which anti-TGFbeta therapy is appropriate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA534815
Entities
People
- Aubie Shaw
Organizations
- Vanderbilt University