TRANSCRIPTIONAL ACTIVATION BY TGF-BETA-1 MEDIATED BY THE DYAD SYMMETRY ELEMENT (DSE) AND THE TPA RESPONSIVE ELEMENT (TRE)

Transforming growth factor β1 (TGFβ1) is a multifunctional regulator of growth and differentiation. However, both cytoplasmatic and nuclear signal transduction mechanisms leading to the biological effects of TGFβ1 are largely unknown. In this report we show, that TGFβ1 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 TGFβ1 in a protein synthesis independent fashion both in quiescent mouse 3T3 fibroblasts, which are growth stimulated by TGFβ1, as well as in mink lung CCL64 (ML-CCL64) epithelial cells, which are growth inhibited by TGFβ1. The PDGF inducible JE gene was induced by TGFβ1 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 TGFβ1 in transient transfection assays in both growth inhibited and growth stimulated cells. These results show that the early genomic responses to TGFβ1 resemble changes in gene expression induced by serum, growth factors and phorbol esters, suggesting common mechanisms of transcriptional activation. © 1990.