Constitutive hypophosphorylation of extracellular signal-regulated kinases-1/2 and down-regulation of c-Jun in human gastric adenocarcinoma

Biochem Biophys Res Commun. 2008 Aug 22;373(2):330-4. doi: 10.1016/j.bbrc.2008.06.025. Epub 2008 Jun 18.

Abstract

Hyperphosphorylation of extracellular signal-regulated protein kinases-1/2 (ERK1/2) is known to promote cancer cell proliferation. We therefore investigated the constitutive phosphorylation levels of ERK1/2 and the expression of its downstream targets c-Fos, c-Jun, and cyclooxygenase-2 (COX-2) in biopsied human gastric cancer tissues. Results showed that ERK1/2 phosphorylation and c-Jun expression were significantly lowered in gastric cancer compared with the non-cancer adjacent tissues. The expression of c-Fos, however, was not altered while COX-2 was significantly up-regulated. To conclude, we demonstrate that hypophosphorylation of ERK1/2 may occur in gastric cancer. Such discovery may have implication in the application of pathway-directed therapy for this malignant disease.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Down-Regulation
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / enzymology*

Substances

  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3