Regulation of epidermal growth factor receptor gene expression by retinoic acid and epidermal growth factor.
In normal rat kidney fibroblasts, retinoic acid increases the level of epidermal growth factor (EGF) binding and synergizes with EGF and transforming growth factor-beta to stimulate anchorage-independent growth. We now demonstrate that retinoids act by increasing the rate of transcription of the EGF receptor gene, resulting in elevated mRNA levels. No effect of retinoic acid on EGF receptor mRNA half-life, measured after actinomycin D treatment, was observed. In the same system, EGF was also able to increase expression of its own receptor through an elevation in mRNA levels. These effects were specific since retinoids and EGF did not alter transcript levels for fibronectin, alpha-tubulin, or beta 2-microglobulin. These results demonstrate that the EGF receptor gene is a target for regulation by multiple growth-stimulating factors.
Department of Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge 02139.
K L
KL
Thompson
M R
MR
Rosner
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D015342:DNA Probes; D012333:RNA, Messenger; D003609:Dactinomycin; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors