Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1

Stats1 and 3 (signal transducers and activators of transcription) can be ac tivated simultaneously, although not necessarily to the same degree or dura tion, by the interaction of cells with the same polypeptide ligand (EGF, PD GF, or high concentrations of IL-6, for example). However, these two stat p roteins can mediate opposing effects on cell growth and survival. Stat1 act ivation slows growth and promotes apoptosis. In contrast, activated Stat3 c an protect cells from apoptosis. Furthermore, a constitutively active form of Stat3, Stat3-C (bridged by S-S linkages between cysteines instead of pho sphotyrosines) can induce cellular transformation of fibroblasts. We have d etermined that fibroblasts transformed by Stat3-C are more resistant to pro apoptotic stimuli than nontransformed cells. Also, to examine the potential opposing roles in apoptosis of Stat1 and Stat3, we studied the cervical ca rcinoma-derived cell line, Me180, which undergoes Stat1-dependent, IFN gamm a -induced apoptosis, Me180 cells that express Stat3-C are protected agains t INF gamma -mediated apoptosis.