title: The effect of Helicobacter pylori CagA on the HER-2 copy number and expression in gastric cancer.
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.
authors.affiliation: Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Sahmyook University, Hwarangro 815, Nowon-gu, Seoul 139-742, South Korea.
authors.forename: Sung Sook
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Department of Medicine, Howard University, Washington, DC 20060, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Department of Medicine, Howard University, Washington, DC 20060, USA.
authors.forename: Duane T
authors.initials: DT
authors.lastname: Smoot
authors.affiliation: Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Kyo Young
authors.initials: KY
authors.lastname: Song
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Cho Hyun
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: wonsang@catholic.ac.kr.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C080866:cagA protein, Helicobacter pylori; C508053:ERBB2 protein, human; C524056:Erbb2 protein, mouse
keywords: CagA; DNA amplification; Gastric cancer; H. pylori; HER-2/neu