项目名称： HDGF2促进肝癌发生发展的分子机制研究

项目编号： No.30872947

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 章平肇

作者单位： 复旦大学

项目金额： 30万元

中文摘要： 肝癌是我国人群最常见的癌症之一，对其发病的分子机制还不甚清楚，也成为当下迫切研究热点。我们研究了肝癌衍生生长因子家族成员HDGF2、HRP-3与肝癌发生发展的关系。HDGF2在肝癌组织中显著上调，超表达HDGF2可使NIH3T3细胞恶性转化，注射裸鼠皮下可以成瘤。通过基因芯片和酵母双杂等技术手段研究HDGF2促肝癌的具体分子机制，HDGF2可以显著上下调多个肿瘤相关基因，在分子水平和mRNA转录、延伸调节因子-IWS1强烈互作。IWS1在肝癌中也是显著上调。另外我们还发现该家族的另外一个成员HRP-3在肝癌中也显著上调的。HRP3可以调节脱巢凋亡来促进肿瘤的在体内和体外的生长。本课题将研究HDGF2、IWS1和HRP-3肝癌临床指标的相关性、互作复合体对靶基因的调控、对各种肝癌细胞株增殖和凋亡的影响。并探讨其作为分子诊断marker和药物靶点的可能性。

中文关键词： HDGF；IWS1；肝癌；增殖；血管新生

英文摘要： Hepatocellular carcinoma (HCC) is one of common malignant tumors in the world, and the global incidence rate has exceeded 1 million per year. China has been always the high incidence of HCC worldwide. The molecular mechanism is largely unknown. In this study, The role of Hatoma-derived growth factor familiy member HDGF2 and HRP-3 in HCC was investigated. HDGF2 was singificantly upregulated in HCC. Overexpression of HDGF2 promotes transformation of NIH3T3 cells. We also explored the molecular mechnism of HDGF2 in HCC. Microarray data showed HDGF2 overexpreesion induced some cancer-related genes. We also domonstrated that HDGF2 physically interacts with IWS1, a mRNA transcriptional and elongation factor. IWS1 was also significantly upregualted in HCC. HRP-3 was also included in this study because It aso also upregualted in HCC. HRP-3 promotes HCC carcinogenesis through regulating anokis,a special type of apoptosis induced by detachment. This project aim in eludicating the clinical corealtion,cell proliferation,apopotosis of HCC of HDGF2,IWS1 and HRP-3, and discussed its potential role of these protein in molecular diagnosis and drug target.

英文关键词： HDGF；IWS1；HCC；proliferation；angiogenesis