Figure 1

Transforming growth factor (TGF)-β has tumor suppressor and oncogenic activities. Acting directly on the mammary epithelium, TGF-β could suppress tumorigenesis through a number of mechanisms, including inhibition of epithelial cell proliferation, induction of apoptosis or senescence in initiated cells, and maintenance of genomic stability. All of these activities require an intact epithelial response to TGF-β. TGF-β can also have pro-oncogenic effects. These may be either direct, or indirect via the stroma. Direct effects include the promotion of the epithelial-mesenchymal transition and invasiveness, and an increase in production of parathyroid hormone-related peptide (PTHrP). These are also dependent on an intact epithelial response system. Indirect effects include the induction of angiogenesis, and suppression of the immune surveillance system. The indirect oncogenic effects are presumed to dominate when epithelial responsiveness to TGF-β is lost.