Epidermal growth factor receptor induced apoptosis: Potentiation by inhibition of Ras signaling

Thorbergur Högnason, Sukalyan Chatterjee, Timothy Vartanian, Rajiv R. Ratan, Krista M. Ernewein, Amyn A. Habib

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Previous studies have shown that certain tumor cell lines which naturally express high levels of the epidermal growth factor receptor (EGFR) undergo apoptosis when exposed to epidermal growth factor. Whether this phenomenon is a direct result of receptor overexpression or some other genetic alteration renders these cells sensitive to apoptosis is yet to be established. We show that experimentally increasing the level of EGFR expression predictably leads to apoptosis in a variety of cell types which requires an active tyrosine kinase but not EGFR autophosphorylation sites. Expression of a dominant negative Ras mutant in EGFR overexpressing cells results in a significant potentiation of EGFR induced apoptosis suggesting that Ras activation is a key survival signal generated by the EGFR. We propose that potentiation of EGFR induced apoptosis by dominant negative Ras results, at least in part, by a block of Akt activation.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalFEBS Letters
Volume491
Issue number1-2
DOIs
StatePublished - Feb 23 2001

Keywords

  • Akt
  • Apoptosis
  • Epidermal growth factor receptor
  • Growth factor
  • Ras
  • Signaling

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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