Helicobacter pylori Eradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter 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 compared cIAP2 mRNA 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 of cIAP2 messenger 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 of cIAP2 mRNA 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 of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month followup after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period. Conclusions: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.
Abstract
Background/Aims: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter 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 compared cIAP2 mRNA 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 of cIAP2 messenger 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 of cIAP2 mRNA 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 of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month followup after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period. Conclusions: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.
참고문헌 (29)
- Nachmias B, "The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer", Semin Cancer Biol, 14, pp.231~243 (2004)
- Tamm I, "Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias", Clin Cancer Res, 6, pp.1796~1803 (2000)
- Conte D, "Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival", Mol Cell Biol, 26, pp.699~708 (2006)
- Wang CY, "NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2and c-IAP1 and c-IAP2 to suppress caspase-8 activation", Science, 281, pp.1680~1683 (1998)
- Miura K, "cIAP2 as a therapeutic target in colorectal cancer and other malignancies", Expert Opin Ther Targets, 13, pp.1333~1345 (2009)
- Esposito I, "Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer", J Clin Pathol, 60, pp.885~895 (2007)
- Maeda S, "Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori", Gut, 50, pp.771~778 (2002)
- Gupta RA, "Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells", J Biol Chem, 276, pp.31059~31066 (2001)
- Liu W, "Down-regulation of HSP70 sensitizes gastric epithelial cells to apoptosis and growth retardation triggered by H. pylori", BMC Gastroenterol, 11, pp.146~ (2011)
- Mannick EE, "Gene expression in gastric biopsies from patients infected with Helicobacter pylori", Scand J Gastroenterol, 39, pp.1192~1200 (2004)
- Valenzuela M, "Helicobacter pyloriinduced loss of survivin and gastric cell viability is attributable to secreted bacterial gamma-glutamyl transpeptidase activity", J Infect Dis, 208, pp.1131~1141 (2013)
- Yanai A, "Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation", J Infect Dis, 188, pp.1741~1751 (2003)
- Li Z, "A possible role of cIAP2 in Helicobacter pylori-associated gastric cancer", Cancer Lett, 313, pp.192~200 (2011)
- Chang CS, "Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma", World J Gastroenterol, 10, pp.2232~2240 (2004)
- Choi J, "Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma", Clin Gastroenterol Hepatol, 12, pp.793~800.e1 (2014)
- Dixon MF, "Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994", Am J Surg Pathol, 20, pp.1161~1181 (1994)
- 강정묵, "CDX1 and CDX2 Expression in Intestinal Metaplasia, Dysplasia and Gastric Cancer", Journal of Korean Medical Science, 26(5), pp.647~653 (2011), 대한의학회
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method", Methods, 25, pp.402~408 (2001)
- 박희평, "Effects of sevoflurane on neuronal cell damage after severe cerebral ischemia in rats", Korean Journal of Anesthesiology, 61(4), pp.327~331 (2011), 대한마취통증의학회
- Uemura N, "Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer", Cancer Epidemiol Biomarkers Prev, 6, pp.639~642 (1997)
- Fukase K, "Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial", Lancet, 372, pp.392~397 (2008)
- Kim YI, "The association between Helicobacter pylori status and incidence of metachronous gastric cancer after endoscopic resection of early gastric cancer", Helicobacter, 19, pp.194~201 (2014)
- Tsai CJ, "Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy", Cancer Epidemiol Biomarkers Prev, 15, pp.272~280 (2006)
- Burz C, "Apoptosis in cancer: key molecular signaling pathways and therapy targets", Acta Oncol, 48, pp.811~821 (2009)
- Roy N, "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases", EMBO J, 16, pp.6914~6925 (1997)
- Deveraux QL, "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases", EMBO J, 17, pp.2215~2223 (1998)
- Kim JY, "Association of polymorphisms in virulence factor of Helicobacter pylori and gastroduodenal diseases in South Korea", J Gastroenterol Hepatol, 29, pp.984~991 (2014)
- Ricci MS, "Reduction of TRAIL-induced Mcl-1and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death.", Cancer Cell, 12, pp.66~80 (2007)
- Smolewski P, "Inhibitors of apoptosis proteins (IAPs) as potential molecular targets for therapy of hematological malignancies", Curr Mol Med, 11, pp.633~649 (2011)
