Ligand-activated thyroid hormone and retinoic acid receptors inhibit growth factor receptor promoter expression

Thyroid hormone (T3) and retinoic acid (RA) receptors mediate ligand-dependent inhibition of epidermal growth factor (EGF) receptor and c-erbB2/neu promoter activities. Ligand-activated T3 and RA receptors act via a 36 bp 5' fragment of the EGF receptor gene in vivo and, in the presence of nuclear extract, bind with high affinity to this region in vitro. Both ligand binding and DNA binding domains of T3 and RA receptors are required for promoter inhibition. When both receptors are expressed in the presence of a single ligand, inhibition is reversed, indicating that the hormone-activated receptor is competed by the unliganded receptor. These results suggest that ligand regulates transcriptional inhibitory functions of the T3 and RA receptors and describe novel regulation of growth factor receptor gene expression.