Differential regulation of EGF-like growth factor genes in human keratinocytes

ErbB signaling increases protein levels of multiple EGF-like growth factors in epithelial cells, To better understand this process, we examined the ef fects of EGF receptor stimulation on the transcription and mRNA stability o f TGF-alpha, amphiregulin (AR), and heparin-binding EGF-like growth factor (HB-EGF) in human keratinocytes, EGF stimulation increased transcription of TGF-alpha, AR and HB-EGF by 3- to 4-fold within 1 to 2 h, However, AR and HB-EGF mRNA levels peaked at 2 h and then rapidly declined, whereas TGF-alp ha transcripts remained elevated for at least 6 h, Actinomycin D decay expe riments yielded the rank order of transcript stability TGF-alpha > AR > HB- EGF. Interestingly, ligand treatment appeared to stabilize TGF-alpha and AR mRNAs, whereas NB-EGF transcripts were destabilized, These data demonstrat e that gene-specific alterations in gene transcription and mRNA stability p lay important roles in the temporal regulation of EGF-like growth factor ge ne expression. (C) 1999 Academic Press.