EGF-induced activation of stat1, stat3, and stat5b is unrelated to the stimulation of DNA synthesis in cultured hepatocytes

Transcription factors of the STAT family have been implicated in regulation of cell proliferation. EGF activates several STAT proteins in liver. We ha ve studied the relationship between STAT activation and the growth-stimulat ory effect of EGF in rat hepatocytes, assessing specific DNA-binding activi ty of STAT proteins in electrophoretic mobility-shift and supershift assays . In freshly isolated hepatocytes, EGF activated Stat1, Stat3, and, particu larly, Stat5b. However, the ability of EGF to produce this activation was r apidly attenuated when the cells were cultured, while the activation by IFN -gamma (Stat1) and IL-6 (Stat3) was sustained. Hepatocytes cultured for 24- 48 h are highly sensitive to the stimulatory effect of EGF on S phase entry . In these cells EGF did not detectably activate Stat1, Stat3, or Stat5b bu t markedly stimulated MAP kinase (Erk1/2), Thus, although EGF has the abili ty to activate several STAT proteins, this did not seem to be part of the m itogenic mechanisms used by the EGF receptor in hepatocytes. (C) 1999 Acade mic Press.