Role of TGF-beta in EGF-induced transformation of NRK cells is sustaining high-level EGF-signaling

We have been isolating and analyzing NRK cell mutants, which fail to transf orm by epidermal growth factor (EGF) and transforming growth factor (TGF)-b eta. One such mutant, R14, can respond to the growth inhibitory signal of T GF-beta to the same extent as parental NRK but fail to respond to the growt h stimulatory signal of EGF, This mutant has a defect in EGF receptor (EGFR ) expression. When R14 mutant expressed a high level of EGFR, however, EGF not only induced proliferation in this mutant but also induced transformati on without the aid of TGF-beta. These findings suggest that the major role of TGF-beta in this transformation system should be to counteract the ligan d-dependent down-regulation of EGFR, thereby sustaining high-level EGF-sign aling. (C) 2000 Federation of European Biochemical Societies.