Immediate early gene responses of NIH 3T3 fibroblasts and NMuMG epithelial cells to TGF beta-1.

Transforming growth factor beta has a wide range of physiological effects on cell growth and metabolism. We have previously reported on the rapid induction of jun transcription factors in TGF beta-treated cells. Here we show that the early genomic response to TGF beta-1 includes activation of a broad spectrum of serum-inducible genes both in NIH 3T3 fibroblasts and in NMuMG epithelial cells, which are growth-stimulated and growth-inhibited by TGF beta, respectively. Of particular interest is the presence of a putative nuclear DNA-binding receptor (N10) and zinc finger transcription factors (Krox 20 and Krox 24) among the TGF beta-induced genes. In addition to the stimulatory effects of TGF beta, expression of a few genes including c-myc is decreased in both types of cells. In cells transformed by neu or ras oncogenes the immediate early mRNA responses to TGF beta are deregulated. Our results suggest that certain transcription factors are required for both positive and negative regulation of cell proliferation by TGF beta, and that their relative concentrations may determine the subsequent cellular responses.