厦大Oncogene发表肝癌研究论文

　　

生物通报道，厦门大学生命科学院俞春东教授课题组近期在肝癌研究方面取得新的进展，相关成果文章Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness公布在最近一期的Nature子刊Oncogene上。

 

文章通讯作者是厦门大学生命科学学院俞春东教授，其早年在中山大学生物学系获学士学位，在厦门大学生物学系获硕士学位。1998年起先后在美国德州大学休斯敦健康科学中心及美国贝勒医学院从事博士及博士后研究，2006年回到厦门大学生命科学学院，主要从事核受体及其共激活子在肝脏代谢及肝脏疾病中的作用及核受体及其共激活子在炎症反应及自身免疫疾病中的作用等研究。

 

该研究发现核受体辅激活因子AIB1（Amplified in breast Cancer 1）在68%肝癌组织以及几种常见的肝癌细胞株中高表达。进一步的研究表明沉默AIB1可抑制肝癌细胞增殖和侵袭，并证明AIB1通过抑制P21蛋白的表达实现其对细胞周期的调控以及通过促进MMP-9的表达来调控细胞的侵袭能力。

 

在肝癌组织中AIB1的表达与细胞生长指示蛋白PCNA的表达呈正相关性，提示AIB1的表达水平具有重要的临床指导意义。该论文首次对转录协同因子AIB1在肝癌发生和发展中的作用进行了系统的研究分析，揭示出AIB1在肝癌发生和发展中具有重要的促进作用，为肝癌的治疗研究提供新思路。

（生物通 小茜）

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

Y Xu1,3, Q Chen2,3, W Li2, X Su1,2, T Chen1, Y Liu1, Y Zhao1 and C Yu1

 

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

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

Correspondence: Dr C Yu, Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China. E-mail: [e-mail]

3These authors contributed equally to this work.

Received 21 September 2009; Revised 1 February 2010; Accepted 18 February 2010; Published online 22 March 2010.

 

【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.