Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma

被引：83

作者：

Kashimoto, Kingo ^{[1
]}

Komatsu, Shuhei ^{[1
]}

Ichikawa, Daisuke ^{[1
]}

Arita, Tomohiro ^{[1
]}

Konishi, Hirotaka ^{[1
]}

Nagata, Hiroaki ^{[1
]}

Takeshita, Hiroki ^{[1
]}

Nishimura, Yukihisa ^{[1
]}

Hirajima, Shoji ^{[1
]}

Kawaguchi, Tsutomu ^{[1
]}

Shiozaki, Atsushi ^{[1
]}

Fujiwara, Hitoshi ^{[1
]}

Okamoto, Kazuma ^{[1
]}

Tsuda, Hitoshi ^{[2
]}

Otsuji, Eigo ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Surg, Div Digest Surg, Kyoto 602, Japan

[2] Natl Canc Ctr, Dept Pathol, Tokyo, Japan

来源：

CANCER SCIENCE | 2012年 / 103卷 / 11期

基金：

日本学术振兴会;

关键词：

SQUAMOUS-CELL CARCINOMA; LINDAU TUMOR-SUPPRESSOR; CANCER; GENE; ADENOCARCINOMA; UBIQUITINATION; MUTATION; PROTEIN; DEGRADATION; METHYLATION;

D O I：

10.1111/j.1349-7006.2012.02407.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family, which is characterized by a conserved RING finger, B-box, and coiled-coil domains, function as important regulators for carcinogenesis. In this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene through overexpression in gastric cancer. We analyzed seven gastric cancer cell lines and 112 primary tumors, which were curatively resected in our hospital between 2001 and 2003. Expression of the TRIM44 protein was detected in gastric cancer cell lines (2/7 cell lines; 29%) and primary tumor samples of gastric cancer (29/112 cases; 25%). Knockdown of TRIM44 expression using several specific siRNAs inhibited the proliferation, migration, and invasion of TRIM44-overexpressing cells. Overexpression of the TRIM44 protein was significantly correlated with an advanced type of macroscopic appearance, lymphatic invasion, and higher recurrence rate. TRIM44-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0038, logrank test) in both intensity and proportion expression-dependent manner. TRIM44 positivity was independently associated with worse outcome in multivariate analysis (P = 0.0233, hazard ratio 3.37 [1.18-9.64]). These findings suggest that TRIM44 plays a crucial role in tumor cell proliferation through its overexpression, and highlight its usefulness as a predictor and potential therapeutic target in gastric cancer. (Cancer Sci 2012; 103: 2021-2026)

引用

页码：2021 / 2026

页数：6

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