TGF-beta and functional differentiation.

A review of the pertinent literature suggests that TGF-beta 1 may play a multifaceted role in functional differentiation of mammary epithelium. Evidence for the expression of TGF-beta 1 RNA and the presence of functional TGF-beta 1 protein in differentiating mammary epithelial cells from a pregnant mouse has been recently reported. The specific role of mammary-epithelial-cell-produced TGF-beta 1 in the differentiating mammary gland is presently unclear. However, several possible functions are suggested from the following observations. Milk protein production is negatively regulated by exogenous TGF-beta 1 during gestational development of the gland but not during lactation. Consistent with reports linking TGF-beta 1 gene expression with mammary gland involution following lactation, overexpression of TGF-beta 1 in the differentiating secretory epithelium leads to premature programmed cell death in the absence of a negative effect on secretory epithelial cell proliferation. A role for TGF-beta 1 in cell cycle control and suppression of malignant progression independent from its inhibitory effect on epithelial cell growth has been demonstrated in keratinocytes. A similar function could provide protection against malignancy in proliferating mammary epithelium and account for TGF-beta 1 suppression of mammary tumorigenesis in transgenic mice overexpressing transforming growth factor alpha (TGF-alpha).