Abstract 3093: Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Amplified in breast cancer 1 (AIB1; SRC-3) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has been identified to play an important role in malignancy of several cancers such as breast and prostate cancers; however, its involvement in the progression of hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the expression and possible role of AIB1 in HCC. Western blot analysis revealed that AIB1 was significantly increased in 15 of 22 HCC samples (68%), whereas only trace amounts of AIB1 were detected in the most matched nontumorous liver tissues. Functional studies on HCC cells demonstrated that AIB1 specific small interfering RNA mediated down-regulation of AIB1 resulted in decreased cell proliferation rate, cell migration/invasion ability, colony formation ability, and tumorigenic potential in nude mice. Marked increase of cell cycle inhibitor p21Cip1/Waf1 expression and dramatic decrease of the expression of phosphorylated Akt, proliferating cell nuclear antigen (PCNA), and matrix metallopeptidase MMP-9 in AIB1 knockdown cells contributed to these phenotypic changes. Consistent with these results, clinical AIB1-positive HCC exhibited higher levels of PCNA protein expression compared with AIB1-negative HCC. Further statistical calculation revealed a positive and tight correlation between the levels of AIB1 protein and PCNA protein in HCC, indicating that AIB1 contributes significantly to HCC cell proliferation. Conclusion: our results demonstrate that AIB1 promotes the progression of human HCC by enhancing cell proliferation and invasiveness, and could be a potential therapeutic target molecule for HCC treatment. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3093.