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

Biochem Biophys Res Commun. 1999 Nov;265(1):214-21. doi: 10.1006/bbrc.1999.1654.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amphiregulin
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Dactinomycin / pharmacology
  • EGF Family of Proteins
  • Epidermal Growth Factor / genetics*
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / physiology*
  • Gene Expression Regulation* / drug effects
  • Glycoproteins / genetics*
  • Growth Substances / genetics*
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Kinetics
  • RNA, Messenger / genetics
  • Transcription, Genetic* / drug effects
  • Transforming Growth Factor alpha / genetics*
  • Transforming Growth Factor alpha / pharmacology

Substances

  • AREG protein, human
  • Amphiregulin
  • EGF Family of Proteins
  • Glycoproteins
  • Growth Substances
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Dactinomycin
  • Epidermal Growth Factor
  • ErbB Receptors