EPIDERMAL GROWTH FACTOR-INDUCED GROWTH-INHIBITION REQUIRES STAT1 ACTIVATION

Epidermal growth factor (EGF) is a mitogen for most epithelial cells. Paradoxically, the growth of some cultured cell lines, containing high numbers of EGF receptors, are inhibited by EGF. Here we demonstrate t hat growth inhibition by EGF in several cell lines correlates with the activation of the signal transducer and activator of transcription (S tat) 1. In contrast, in normal fibroblasts and several cell lines that are growth stimulated by EGF, we observed no or very transient activa tion of Stat1. A causal association between Stat1 activation by EGF an d growth inhibition was suggested by the expression of a dominant-nega tive Stat1 in A431 cells, resulting in the loss of Stat1 DNA binding a nd concomitant resistance to growth inhibition by EGF. We conclude tha t, in the cells examined, POP-induced arrest of growth requires activa ted Stat1.