Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer

// Jing Shi 1, * , Wei Liu 1, * , Fang Sui 1 , Rong Lu 1 , Qingyuan He 2 , Qi Yang 1 , Hongjun Lv 1 , Bingyin Shi 1 , Peng Hou 1 1 Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an 710061, The People’s Republic of China 2 Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an 710061, The People’s Republic of China * These authors have contributed equally to this work Correspondence to: Peng Hou, e-mail: phou@mail.xjtu.edu.cn Keywords: gastric cancer, AIB1, genomic amplification, poor prognosis, signaling pathways Received: October 23, 2014      Accepted: April 17, 2015      Published: April 29, 2015 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.