Upregulation of recepteur d'origine nantais tyrosine kinase and cell invasiveness via early growth response-1 in gastric cancer cells

J Cell Biochem. 2012 Apr;113(4):1217-23. doi: 10.1002/jcb.23454.

Abstract

Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in carcinogenesis of epithelial tumors. RON expression was induced by the tumor promoter, phorbol 12-myristate 13-acetate (PMA), in gastric adenocarcinoma AGS cells. Studies with deleted and site-directed mutagenesis of Egr-1 promoter and with expression vectors encoding Egr-1 confirmed that Egr-1 is essential for RON expression. In addition, AGS cells pretreated with PMA showed remarkably enhanced invasiveness, which was partially abrogated by siRNA-targeted RON and Egr-1. These results suggest that tumor promoter induces RON expression via Egr-1, which, in turn, stimulates cell invasiveness in AGS cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA Primers
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / physiology*
  • Humans
  • Mutagenesis, Site-Directed
  • Neoplasm Invasiveness*
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Up-Regulation*

Substances

  • DNA Primers
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • RNA, Small Interfering
  • RON protein
  • Receptor Protein-Tyrosine Kinases