TGF-beta in mammary gland development and breast cancer.

TGF-beta is now recognized as an important factor regulating normal mammary gland development as well as breast cancer. In development, TGF-beta regulates branching morphogenesis and differentiation by acting on both epithelial and stromal cells. TGF-beta also regulates apoptosis and matrix remodeling during involution at the end of the pregnancy cycle. TGF-beta has biphasic effects on tumor progression, acting as a tumor suppressor in early stages of cancer and promoting invasion and metastasis at later stages. Furthermore, TGF-beta may play a role in tumor progression through effects on the microenvironment. The tumor promoting effects of TGF-beta may provide a therapeutic target for late stage breast cancer via TGF-beta antagonists like the soluble receptors recently described. Future experiments will uncover the precise mechanisms of TGF-beta action in development and neoplastic disease providing more opportunities for prevention and treatment of breast disease.