Transcriptional activation by TGF beta 1 mediated by the dyad symmetry element (DSE) and the TPA responsive element...

Transforming growth factor beta 1 (TGF beta 1) is a multifunctional regulator of growth and differentiation. However, both cytoplasmatic and nuclear signal transduction mechanisms leading to the biological effects of TGF beta 1 are largely unknown. In this report we show, that TGF beta 1 induces the expression of the immediate early genes c-jun and jun B, that encode trans-acting factors regulating transcription of a variety of genes in response to growth factors and phorbol esters. The jun genes are induced by TGF beta 1 in a protein synthesis independent fashion both in quiescent mouse 3T3 fibroblasts, which are growth stimulated by TGF beta 1, as well as in mink lung CCL64 (ML-CCL64) epithelial cells, which are growth inhibited by TGF beta 1. The PDGF inducible JE gene was induced by TGF beta 1 in 3T3, but not in ML-CCL64 cells. Furthermore, we show that chimaeric reporter-CAT constructs containing the TPA responsive element (TRE) or the dyad symmetry element (DSE) are activated by TGF beta 1 in transient transfection assays in both growth inhibited and growth stimulated cells. These results show that the early genomic responses to TGF beta 1 resemble changes in gene expression induced by serum, growth factors and phorbol esters, suggesting common mechanisms of transcriptional activation.