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

Oncogene volume 29, pages 3386–3397 (2010)Cite this article

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Abstract

Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has an important role in malignancy of several cancers such as breast and prostate cancers. However, its involvement in human hepatocellular carcinoma (HCC) progression remains unclear. Here, we found that AIB1 protein was overexpressed in 23 of 34 human HCC specimens (68%). Down-regulation of AIB1 reduced HCC cell proliferation, migration, invasion, colony formation ability and tumorigenic potential in nude mice. These phenotypic changes caused by AIB1 knockdown correlated with increased expression of the cell cycle inhibitor p21Cip1/Waf1 and decreased Akt activation and the expression of proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase MMP-9. In agreement with these findings, clinical AIB1-positive HCC expressed higher levels of PCNA than AIB1-negative HCC. A positive correlation was established between the levels of AIB1 protein and PCNA protein in HCC, suggesting that AIB1 may contribute to HCC cell proliferation. In addition, MMP-9 expression in AIB1-postive HCC was significantly higher than that in AIB1-negative HCC, suggesting that AIB1-postive HCC may be more invasive. Collectively, our results show that overexpression of AIB1 promotes human HCC progression by enhancing cell proliferation and invasiveness. Therefore, AIB1 is a master regulator of human HCC growth and might be a useful molecular target for HCC prognosis and treatment.

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Acknowledgements

We thank Dr Li Qin for the MMP-9-promoter/reporter plasmid and Dr Jianming Xu for critical reading of the article. This work was supported by Grants from National Basic Research Program of China (973 Program, 2008CB517311 and 2009CB522200), National Natural Science Foundation of China (30600566 and 30770455), 111 Project (06016), and the Science Planning Program of Fujian Province (2009J1010).

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  1. Y Xu and Q Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China

    Y Xu, X Su, T Chen, Y Liu, Y Zhao & C Yu

  2. The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

    Q Chen, W Li & X Su

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Correspondence to C Yu.

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Xu, Y., Chen, Q., Li, W. et al. Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness. Oncogene 29, 3386–3397 (2010). https://doi.org/10.1038/onc.2010.90

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