title: The roles of REIC gene and its encoding product in gastric carcinoma.
abstract: REIC is downregulated in immortalized cell lines compared with the parental normal counterparts. It may inhibit colony formation, tumor growth and induce apoptosis. Here, gastric carcinoma or epithelial cells transfected with REIC-expressing plasmid, its siRNA or treated with recombinant REIC were subjected to the phenotypes' measurement or related molecules' detection. REIC expression was examined in gastric carcinomas by RT-PCR, western blot and immunohistochemistry. REIC overexpression or treatment resulted in a low karyoplasmic ratio and proliferation, G₁ arrest, high apoptosis, low migration, invasion or lamellipodia formation in AGS cells. REIC knockdown caused the opposite in GES-1 cells. Anti-REIC antibody blocked the effects of REIC overexpression on proliferation, G₁/S progression and apoptosis. Ectopic REIC expression downregulated the expression of β-catenin, phosphorylated S6K (Thr389), phosphorylated Akt1/2/3 (Ser473), cyclin D2 and E, WAVE2 and upregulated phosphorylated mTOR (Ser2448) expression and the mRNA level of Akt1, Akt2, mTOR, Raptor and Rictor in AGS cells. REIC expression was negatively associated with tumor size, lymph node metastasis, dedifferentiation or poor prognosis of carcinoma. The serum REIC level was significantly higher in healthy individuals than the carcinoma patients and inversely linked to tumor size by ELISA. The possible mechanisms underlying the forced REIC overexpression or recombinant REIC mediated the reversal of the aggressive phenotypes of gastric carcinoma cells are to downregulate β-catenin and WAVE2 expression and to alter other related target proteins. Downregulated REIC expression was closely linked to aggressive behaviors and poor prognosis of gastric carcinoma.
authors.affiliation: Department of Pathophysiology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xu
authors.forename: Pu
authors.initials: P
authors.lastname: Xia
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Xiao-cui
authors.initials: XC
authors.lastname: Nie
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Xing
authors.forename: Yun-peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines; D056742:Cyclin D2 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D000077209:Decitabine; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics* / Q000276:immunology; D009361:Neoplasm Invasiveness / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018925:Chemokines; D056742:Cyclin D2; D019927:Cyclin E; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051300:Wiskott-Aldrich Syndrome Protein Family; D051176:beta Catenin; D000077209:Decitabine; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2; D001374:Azacitidine