title: Suppression of tumor necrosis factor receptor-associated protein 1 expression induces inhibition of cell proliferation and tumor growth in human esophageal cancer cells.
abstract: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a molecular chaperone involved in multidrug resistance and antiapoptosis in some human tumors, but its regulatory mechanisms have not been revealed in esophageal squamous cell carcinoma (ESCC). In this study, 138 specimens of ESCC were analyzed. TRAP1 was overexpressed in ESCC, particularly in poorly differentiated tumors. To further explore the molecular regulatory mechanism, we constructed specific small interfering RNA-expressing vectors targeting Trap1, and knocked down Trap1 expression in the esophageal cancer cell lines ECA109 and EC9706. Knockdown of Trap1 induced increases in reactive oxygen species and mitochondrial depolarization, which have been proposed as critical regulators of apoptosis. The cell cycle was arrested in G2/M phase, and in vitro inhibition of cell proliferation was confirmed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and bromodeoxyuridine assays. Furthermore, re-expression of TRAP1 in Trap1 small interfering RNA-transfected ESCC cells restored cell proliferation and cell apoptosis. Bioluminescence of subcutaneously xenografted ESCC tumor cells demonstrated significant inhibition of in vivo tumor growth by Trap1 knockdown. This study shows that TRAP1 was overexpressed in most patients with ESCC, and caused an increase in antiapoptosis potency. TRAP1 may be regarded as a target in ESCC biotherapy.
authors.affiliation: Molecular Oncology Department of Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Sui
authors.forename: Fan-Dong
authors.initials: FD
authors.lastname: Meng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Li-Ye
authors.initials: LY
authors.lastname: Fu
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018841:HSP90 Heat-Shock Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C092306:TRAP1 protein, human
keywords: apoptosis; cell proliferation; esophageal squamous cell carcinoma (ESCC); tumor growth; tumor necrosis factor receptor-associated protein 1 (TRAP1)