TRANSFORMING GROWTH FACTOR-BETA-1 AS A SIGNAL FOR INDUCTION OF CELL-DEATH BY APOPTOSIS

Cell death by apoptosis is a major determinant of growth of normal tissues an tumours. The present study aimed to elucidate signal factors involved in its regulation. Epithelial cells in control liver, during regression of cyproterone acetate induced liver hyperplasia, in liver (pre)neoplasia and in uterus undergoing apoptosis in vivo show immunostaining for transforming growth factor beta1 (TGF-beta1) as detected by anti-pre(266-278) TGF-beta1 antibodies. Positive immunostaining is also seen in a few intact cells of hyperplastic, regressing liver apparently preparing for apoptosis, but is virtually not found in hepatocytes of normal or growing liver nor in cells undergoing death by necrosis. Recombinant latency associated protein (rLAP, dimer of the pro-region non-covalently associated with the mature region) complex and mature TGF-beta1 induce apoptosis in isolated hepatocytes cultured in vitro. These findings suggest an involvement of TGF-beta1 in the induction of apoptosis in certain epithelia in vivo.