Balance between activated-STAT and MAP kinase regulates the growth of human bladder cell lines after treatment with epidermal growth factor

Epidermal growth factor (EGF) is a potent mitogen, and its action is mediat ed by MAP kinase (MAPK). Reportedly EGF activates STAT, induces the express ion of p21(waf1), and subsequently inhibits the growth of several types of cancer cells. In this study, we used human bladder cancer cells (T24 and RT 4), immortalized non-tumorigenic human urothelial cells (1T-1, 1T-2, and 1T -3), and epidermal carcinoma cells (A431). EGF inhibited the growth of T24 and A431, and stimulated the growth of 1T-1, 1T-3 and 1T-2, but did not aff ect the growth of RT4. EGF activated MAPK strongly in 1T-1, and slightly in A431, T24, 1T-2, and 1T-3 but marginally in RT4. We detected the activatio n of STAT in T24, 1T-3 and A431 after EGF treatment. EGF enhanced the expre ssion of p21(waf1) mRNA in T24, 1T-2, 1T-3 and A431, and activated the p21( waf1) promoter in T24 cells. These results suggest that i) EGF inhibits the growth of T24 cells via induction of p21(waf1) mediated by STAT, and ii) t he balance between the STAT-induced p21(waf1) and MAPK activities regulates the growth of human bladder cells after EGF treatment.