The role of TGF-beta signaling in mammary tumor metastasis.

摘要

This project focuses on understanding the role of TGF-beta signaling in mammary gland development, tumorigenesis and metastasis. In this dissertation I utilize several different mouse models of mammary tumorigenesis to elucidate the complex role of TGF-beta signaling in mammary tumor metastasis. Using a dominant-negative and conditional knockout approach, the gene encoding the type II TGF-beta receptor, Tgfbr2, was deleted in the mammary epithelium (DNIIR and Tgfbr2MGKO, respectively). These mice were mated to the MMTV-PyVmT and MMTV-neu transgenic mouse models of mammary tumorigenesis to determine the effects of loss of TGF-beta signaling on mammary tumor metastasis. In short, our studies support a tumor suppressive role for epithelial TGF-beta signaling in mammary gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-beta signaling in the carcinoma cells.