TGF-BETA-1 INHIBITION OF TRANSIN STROMELYSIN GENE-EXPRESSION IS MEDIATED THROUGH A FOS BINDING SEQUENCE

Transforming growth factor β1 (TGF-β1) inhibits the growth factor and oncogene induction of transin/stromelysin, a secreted matrix-degrading metalloprotease. We demonstrate that a 10 bp element in the transin promoter is required for the TGF-β1 inhibitory effects and that this sequence is conserved in the promoter regions of several other TGF-β1-inhibited genes. The TGF-β1 inhibitory element (TIE) specifically binds a nuclear protein complex from TGF-β1-stimulated rat fibroblasts. Interestingly, this complex contained the c-fos proto-oncogene product, Fos, and induction of Fos expression was required for the inhibitory effect of TGF-β1 on transin gene expression. These results suggest that TGF-β1 inhibition of gene expression is mediated by the binding of a Fos-containing protein complex to the TIE promoter sequences. © 1990.