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).
Smith
G H
GH
Oncogenetics Section, National Cancer Institute, Bethesda, Maryland 20892-1750, USA. SmithG@ltiblp.nci.nih.gov
D000818:Animals; D001940:Breast / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta