Helicobacter pyloriEradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis.
OBJECTIVE
To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis afterHelicobacter pylori(HP) infection and after HP eradication.


METHODS
We divided non-cancer patients into four groups according to the status of HP infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We comparedcIAP2mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression ofcIAP2messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferasemediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy.


RESULTS
The expression ofcIAP2mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/ IM(-) groups (p<0.005). In the HP eradication group, the expression ofcIAP2mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period.


CONCLUSIONS
The expression ofcIAP2increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression ofcIAP2and suppressed cell apoptosis.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Hyuk
H
Yoon
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Sang Gyun
SG
Kim
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Bo Kyoung
BK
Kim
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
Eun
E
Shin
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Nayoung
N
Kim
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Hyuk-Joon
HJ
Lee
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Gyeong Hoon
GH
Kang
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Hyun Chae
HC
Jung
D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D063646:Carcinogenesis / Q000235:genetics*; D002277:Carcinoma / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D017291:Clarithromycin / Q000627:therapeutic use; D015536:Down-Regulation; D000069916:Endoscopic Mucosal Resection; D005757:Gastritis, Atrophic / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008679:Metaplasia; D009367:Neoplasm Staging; D009853:Omeprazole / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D051034:Inhibitor of Apoptosis Proteins; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D000658:Amoxicillin; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D017291:Clarithromycin; D009853:Omeprazole
Cellular inhibitor of apoptosis protein 2; Gastric carcinogenesis; Helicobacter pylori