RRC ID 42388
著者 Chen J, Röcken C, Hoffmann J, Krüger S, Lendeckel U, Rocco A, Pastorekova S, Malfertheiner P, Ebert MP.
タイトル Expression of carbonic anhydrase 9 at the invasion front of gastric cancers.
ジャーナル Gut
Abstract BACKGROUND:Carbonic anhydrase IX (MN/Ca9) catalyses the reversible metabolism of carbon dioxide to carbonic acid and has also been linked to malignant transformation and hypoxia in various cancers.
AIMS:To assess the expression and biological role of Ca9 in gastric cancer.
METHODS:Using gastric cancer cell lines and tissues, we studied expression of Ca9 by western blot analysis, immunohistochemistry, and polymerase chain reaction. Biological changes after Ca9 transfection and after treatment with 5'-azadeoxycytidine were also analysed in cancer cell lines.
RESULTS:Non-cancerous tissues strongly expressed Ca9 with membranous localisation. In contrast, Ca9 expression was frequently lost in gastric cancers (p<0.001). However, gastric cancers that retained Ca9 expression in cancer cells exhibited a shorter postoperative survival (p = 0.028). In vitro analysis revealed that loss of Ca9 expression in gastric cancer cell lines was restored after treatment with 5'-azadeoxycytidine and was associated with increased invasion (p<0.01). Moreover, AGS cells transfected with Ca9 exhibited significantly increased cell proliferation (p<0.05).
CONCLUSIONS:A subgroup of gastric cancers retain Ca9 expression in cancer cells at the invasion front. While loss of Ca9 expression is regulated in part by methylation, re-expression of Ca9 is associated with increased invasion, supporting the hypothesis that increased Ca9 expression may contribute to invasion and thus advanced disease and tumour progression in a subset of gastric cancers.
巻・号 54(7)
ページ 920-7
公開日 2005-7-1
DOI 10.1136/gut.2004.047340
PII 54/7/920
PMID 15951534
PMC PMC1774603
MeSH Adult Aged Aged, 80 and over Antigens, Neoplasm / genetics Antigens, Neoplasm / metabolism* Biomarkers, Tumor / metabolism* Blotting, Western / methods Carbonic Anhydrase IX Carbonic Anhydrases / genetics Carbonic Anhydrases / metabolism* Cell Proliferation Female Humans Isoenzymes / metabolism Male Methylation Middle Aged Neoplasm Invasiveness Neoplasm Proteins / metabolism Prognosis Stomach Neoplasms / enzymology* Stomach Neoplasms / pathology Transfection Tumor Cells, Cultured
IF 19.819
引用数 70
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 MKN45(RCB1001) MKN28(RCB1000)