Glycine-extended gastrin inhibits apoptosis in colon cancer cells via separate activation of Akt and JNK pathways

Ian L P Beales, O Ogunwobi

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30 Citations (Scopus)


Glycine-extended gastrin (G-Gly) is produced by colon cancers and has growth promoting and anti-apoptotic effects in the colonic epithelium. We have examined the anti-apoptotic effects of G-Gly and the signal transduction pathways involved. G-Gly stimulated HT-29 cell proliferation in a concentration dependent manner and inhibited serum-starvation and celecoxib-induced apoptosis. Inhibition of signalling via c-Jun NH2-terminal kinase (JNK) with SP600125 or PI3-kinase/Akt with LY294002 abolished the effects of G-Gly. G-Gly significantly increased phosphorylation of both JNK and Akt. The JAK2 inhibitor AG490 abolished the anti-apoptotic effect of G-Gly and inhibited phosphorylation of Akt but not of JNK. G-Gly stimulated tyrosine phosphorylation of JAK2. G-Gly-increased activation of AP-1 was JNK-dependant and activation of STAT3 was JAK2-dependant. We conclude that G-Gly promotes growth and inhibits apoptosis in colon cancer cells. These effects are mediated via the JAK2, PI3-kinase/Akt and JNK pathways. Activation of JAK2 is upstream of Akt but not of JNK.
Original languageEnglish
Pages (from-to)140-149
Number of pages10
JournalMolecular and Cellular Endocrinology
Issue number1-2
Publication statusPublished - 9 Mar 2006


  • Anthracenes
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Chromones
  • Colonic Neoplasms
  • Gastrins
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Janus Kinase 2
  • Morpholines
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Pyrazoles
  • STAT3 Transcription Factor
  • Signal Transduction
  • Sulfonamides
  • Transcription Factor AP-1
  • Tyrosine
  • Tyrphostins

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