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-beta 2 inhibited the growth of normal human keratinocytes and their SV40-transformed counterpart in a dose dependent manner. Both normal and SV-40 transformed keratinocytes accumulated in G1 when treated with TGF-beta s. The hyperphosphorylated form of Rb gene product (RB) was reduced by TGF-beta s in normal keratinocytes. In contrast, phosphorylation 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 target of action for TGF-beta s and that additional factors or pathways may be involved in mechanisms of the growth inhibition.