GROWTH-INHIBITION OF SV40-TRANSFORMED HUMAN KERATINOCYTES BY TGF-BETA-S IS NOT LINKED TO DEPHOSPHORYLATION OF THE RB GENE-PRODUCT

We found that transforming growth factor beta 1 (TGF-beta 1) and TGF-b eta 2 inhibited the growth of normal human keratinocytes and their SV4 0-transformed counterpart in a dose dependent manner. Both normal and SV-40 transformed keratinocytes accumulated in G1 when treated with TG F-beta s. The hyperphosphorylated form of Rb gene product (RB) was red uced by TGF-beta s in normal keratinocytes. In contrast, phosphorylati on of RB was not essentially affected in SV-40 transformed cells. This uncoupling of growth kinetics and phosphorylation states of RB in SV- 40 transformed keratinocytes suggests that RB is not the primary targe t of action for TGF-beta s and that additional factors or pathways may be involved in mechanisms of the growth inhibition. (C) 1994 Academic Press, Inc.