title: Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer.
abstract: Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer. Our data demonstrated that AIB1 was significantly up-regulated in gastric cancer tissues as compared with control subjects. Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects. AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival. AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation, invasiveness and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell proliferation, survival and invasiveness through modulating major signaling pathways such as ErbB and Wnt/β-catenin pathways. Collectively, these findings suggest that AIB1 plays an important role in the pathogenesis of gastric cancer and represents a potential prognostic marker and therapeutic target for this cancer.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sui
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, The People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005784:Gene Amplification; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D014162:Transfection
chemical_list: C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3
keywords: AIB1; gastric cancer; genomic amplification; poor prognosis; signaling pathways