Transforming growth factor-beta and breast cancer - Lessons learned from genetically altered mouse models

Transforming growth factor (TGF)-betas are plausible candidate tumor suppre ssors in the breast. They also have oncogenic activities under certain circ umstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-beta action in the context of the whole animal. Overexpression of TGF-beta can suppress tumorigenesis in the mamma ry gland, raising the possibility that use of pharmacologic agents to enhan ce TGF-beta function locally might be an effective method for the chemoprev ention of breast cancer. Conversely, loss of TGF-beta response increases sp ontaneous and induced tumorigenesis in the mammary gland. This confirms tha t endogenous TGF-betas have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-beta receptors seen in some human breast hyperplasias may play a causal role in tumor development.