The effect of Helicobacter pylori CagA on the HER-2 copy number and expression in gastric cancer

Jung Ho Shim, Jung Hwan Yoon, Sung Sook Choi, Hassan Ashktorab, Duane T. Smoot, Kyo Young Song, Suk Woo Nam, Jung Young Lee, Cho Hyun Park, Won Sang Park

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We investigated whether Helicobacter pylori (H. pylori) CagA contributes to the DNA copy change and mRNA transcript expression of the HER-2 gene and, consequently, affects HER-2 protein expression to evaluate the significance of CagA and HER-2 amplification in gastric cancer. We used the AGS and MKN1 gastric cancer and HFE-145 immortalized non-neoplastic gastric mucosa cell lines. We also confirmed the effects of CagA on HER-2 expression in human gastric cancer tissues and gastric mucosal tissues of H. pylori infected C57BL/6 mice. Ectopic CagA expression in AGS, MKN1 and HFE-145 cells showed a significant increase in HER-2 gene copy number and expression. The gastric mucosae of H. pylori infected C57BL/6 mice also showed increased HER-2 DNA copy number and protein expression. In addition, CagA expression was detected in 17 (56.7%) of 30 gastric cancer tissues, and eight (47%) of them showed HER-2 DNA amplification of more than two-fold. In immunohistochemistry, HER-2 overexpression was detected in 12 (40%) of 30 gastric cancers and a positive correlation was observed among DNA copy number, the mRNA transcript, and protein expression of the HER-2 gene in gastric cancer (P<. 0.05). These results suggest that H. pylori CagA may induce overexpression of the HER-2 protein by increasing HER-2 DNA and mRNA copy number.

Original languageEnglish (US)
Pages (from-to)288-296
Number of pages9
JournalGene
Volume546
Issue number2
DOIs
StatePublished - Aug 10 2014
Externally publishedYes

Keywords

  • CagA
  • DNA amplification
  • Gastric cancer
  • H. pylori
  • HER-2/neu

ASJC Scopus subject areas

  • Genetics

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