Fibroblast TGF-Beta Signaling in Breast Development and Cancer
Annual summary rept. 15 Aug 2009-14 Aug 2012
VANDERBILT UNIV NASHVILLE TN
Pagination or Media Count:
Hypothesis This proposal will address the hypothesis that TGF 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 TGF signaling within stromal cells on mammary gland development and 2 determine the effect of loss of TGF 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 TGF receptor TGFBRII, which is required for TGF signaling. Cre recombinase driven by Fibroblast-Specific Protein FSP1 and Pro-Collagen I 2 will delete TGFBRII within fibroblasts. To understand the normal biology of fibroblast TGF 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 TGF signaling in fibroblasts in the intact mammary gland. Since TGF can promote or suppress cancer, understanding the roles of fibroblast TGF signaling in breast cancer will allow us to identify patients for which anti-TGF therapy is appropriate.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research