Egr-1 promotes cell proliferation and invasion by increasing β-catenin expression in gastric cancer

Dig Dis Sci. 2013 Feb;58(2):423-30. doi: 10.1007/s10620-012-2356-4. Epub 2012 Aug 24.

Abstract

Background: Abnormal expression of early growth response gene 1 (Egr-1) and β-catenin may play a crucial role in the development and progression of human cancer. However, little is known about the expression and underlying molecular mechanisms in which Egr-1 and β-catenin are involved in the development and progression of gastric cancer.

Aims: The purpose of this study was to elucidate the potential relationship between Egr-1 and β-catenin expression in gastric cancer, which contributes to finding new molecular carcinogenesis as a potential therapeutic target for gastric cancer.

Methods: In a sample of 102 cases of human gastric cancer, the expression of Egr-1 and β-catenin was detected using immunohistochemistry. Egr-1 gene was transfected into gastric cancer SGC7901 cells and its role in proliferation and cell invasion was detected by MTT assay, flow cytometry, wound-healing and transwell invasion assay. Western blot analysis was used to study the expression of β-catenin and cyclin D1 proteins.

Results: Upregulated Egr-1 and β-catenin protein expression were strongly correlated with cancer progression and depth of invasion in gastric cancer. β-catenin, present mainly in cytoplasmic and nucleus of gastric cancer cells, was also positively correlated with Egr-1 expression in gastric cancer. Furthermore, the overexpression of Egr-1 upregulated β-catenin expression level, promoted cell proliferation, increased cell population in S-phase and enhanced gastric cancer cell migration and invasion in vitro.

Conclusions: Egr-1 might contribute to gastric cancer proliferation and invasion through activation of the β-catenin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Disease Progression
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology
  • Signal Transduction / physiology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Transfection
  • Up-Regulation / physiology
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • beta Catenin