| Literature DB >> 24879917 |
Jung Ho Shim1, Jung Hwan Yoon2, Sung Sook Choi3, Hassan Ashktorab4, Duane T Smoot4, Kyo Young Song1, Suk Woo Nam2, Jung Young Lee2, Cho Hyun Park1, Won Sang Park5.
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.Entities:
Keywords: CagA; DNA amplification; Gastric cancer; H. pylori; HER-2/neu
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Year: 2014 PMID: 24879917 PMCID: PMC4286173 DOI: 10.1016/j.gene.2014.05.064
Source DB: PubMed Journal: Gene ISSN: 0378-1119 Impact factor: 3.688