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

Jing Shi,Hongjun Lv,Qingyuan He,Bingyin Shi,Qi Yang,Rong Lu,Wei Liu,Peng Hou,Fang Sui

doi:10.18632/oncotarget.3852

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.

Highlights

Gastric cancer is one of the most common malignancies and the mortality remains the second leading cause for cancer-related deaths worldwide [1]
Amplified in breast cancer 1 (AIB1), is a member of the p160 steroid receptor coactivator (SRC) family [11], which interacts with nuclear receptors (NR) such as estrogen receptor (ER) and androgen receptor (AR), as well as www.impactjournals.com/oncotarget other transcription factors such as E2F1 [12], activator protein-1 (AP-1) [13], nuclear factor-kB (NF-kB) [14] and PEA3 [15] to enhance their effects on target gene transcription
Further analysis indicated that copy number of AIB1 gene in gastric cancer tissues was significantly higher than control subjects (P < 0.0001)

Summary

Introduction

Gastric cancer is one of the most common malignancies and the mortality remains the second leading cause for cancer-related deaths worldwide [1]. AIB1 down-regulation significantly reduced in vitro and in vivo oncogenic potential of gastric cancer cells through modulating major signaling pathways. Further analysis indicated that copy number of AIB1 gene in gastric cancer tissues was significantly higher than control subjects (P < 0.0001).

Results

Conclusion