title: Differential regulation of EGF-like growth factor genes in human keratinocytes.
abstract: ErbB signaling increases protein levels of multiple EGF-like growth factors in epithelial cells. To better understand this process, we examined the effects of EGF receptor stimulation on the transcription and mRNA stability of 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-alpha transcripts remained elevated for at least 6 h. Actinomycin D decay experiments yielded the rank order of transcript stability TGF-alpha > AR > HB-EGF. Interestingly, ligand treatment appeared to stabilize TGF-alpha and AR mRNAs, whereas HB-EGF transcripts were destabilized. These data demonstrate that gene-specific alterations in gene transcription and mRNA stability play important roles in the temporal regulation of EGF-like growth factor gene expression.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Stoll
authors.forename: J T
authors.initials: JT
authors.lastname: Elder
mesh_terms: D000328:Adult; D066258:Amphiregulin; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000494:pharmacology
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors