STEM-CELLS IN BREAST EPITHELIA

The rodent and human nonpregnant mammary glands contain epithelial, in termediate and myoepithelial cells which have all been isolated as cel l lines in vitro. Transforming growth factor-alpha (TGF alpha) and bas ic fibroblast growth factor (bFGF) are produced by myoepithelial cells and can stimulate the growth of intermediate stem cells in vitro, Epi thelial and intermediate cells behave like stem cells in vitro, since they can differentiate into alveolar-like and myoepithelial cells. The myoepithelial differentiation pathway is associated with the early ex pression of a calcium-binding regulatory protein called p9Ka and the p rotease, Cathepsin D. Myoepithelial cells are also present in benign l esions but not in malignant mammary carcinomas of rats or humans, whos e resultant cell lines fail to differentiate completely along the myoe pithelial cell pathway. Loss of the myoepithelial cell in some invasiv e carcinomas may be compensated, at least in part, by changes in malig nant cells. Overexpression of TGF alpha and/or erbB receptors may redu ce the requirement for TGF alpha, whilst ectopic production of bFGF an d its receptors and p9Ka/Cathespin D may assist in tumorigenesis and i n metastasis, respectively. Thus compensation for, or retention of, mo lecules potentially involved in the differentiation of mammary cells m ay be a mechanism by which malignancy progresses in some human invasiv e carcinomas.