title: Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma.
abstract: 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, log-rank 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.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kingo
authors.initials: K
authors.lastname: Kashimoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arita
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeshita
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Shoji
authors.initials: S
authors.lastname: Hirajima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C540677:TRIM44 protein, human; D000070584:Tripartite Motif Proteins