Modulation of transforming growth factor alpha-dependent expression of epidermal growth factor receptor gene by transforming growth factor beta, triiodothyronine, and retinoic acid

We have investigated the actions of transforming growth factor (TGF) type α on epidermal growth factor (EGF) receptor mRNA expression in MDA-468 human mammary carcinoma cells in serum-free media. We found that exposure of MDA-468 cells to TGFα results in elevated levels of EGF receptor mRNA. This increase in mRNA accumulation showed time and dose dependence. Addition of TGFβ1 enhanced the accumulation of EGF receptor mRNA induced by TGFα in a time and dose-dependent manner. We also found that triiodothyronine at physiological concentrations exerts synergistic control on the action of TGFα alone, or in association with TGFβ1, on EGF receptor mRNA expression. Similarly, retinoic acid treatment also enhanced in a time- and dose-dependent manner the TGFα-dependent response of EGF receptor mRNA and acted synergistically with TGFβ1. The results described here suggest that optimum regulation of EGF receptor gene expression by TGFα is a complex process involving synergistic interactions with heterologous growth factors and hormones.