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DPC4抑癌基因转染胰腺癌细胞蛋白质组的改变

DPC4抑癌基因转染胰腺癌细胞蛋白质组的改变
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  • 批准号:30270599
  • 批准年度: 2005年
  • 学科分类:消化系统肿瘤(H1617) |
  • 项目负责人:陈杰
  • 负责人职称:主任医师
  • 依托单位:中国医学科学院
  • 资助金额:19万元
  • 项目类别:面上项目
  • 研究期限:2003年01月01日 至 2005年12月01日
  • 中文关键词: DPC4;抑癌基因;胰腺癌;蛋白质组;改变
  • 英文关键词:pancreatic carcinoma;proteomics;DPC4;INK4a/ARF;tumor suppress gene

项目摘要

中文摘要

用蛋白质组技术检测抑癌基因DPC4转染胰腺癌细胞后,其蛋白表达谱的改变,结合DPC4对细胞生物学特性的影响,寻找DPC4基因下游的靶基因及靶蛋白,阐明DPC4基因的功能及作用机制,探讨TGF-β-Smad4信号通路中蛋白质调节及变化规律,以及DPC4基因作为胰腺癌基因治疗的可行性。

英文摘要

As a forbbiden disease with high mortality, pancreatic carcinoma is hard to cure. This study focus on the proteomics, tumor suppress gene (DPC4 and INK4a/ARF), in order to search the biomarkers for treatment. Three hundreds and two proteins were identified from frozen tissue of 12 human pancreas by proteomics. The composite of these proteins, their possible biological functions were analysed. This paper paved the way for further studies on pancreatic disease. There was a high ratio of loses of DPC4 tumor suppress gene in pancreatic carcinomas, transfection of DPC4 cDNA to pancreatic carcinoma cell line, P2, will suppress the growth of carcinoma, the transfected cell had a higher G1 phase percentage than their control cells. Tumors were suppressed in transplantation of nude mice. Eight proteins, which were up or down regulated after DPC4 transfection were identified, although, their roles in tumor suppression were not comfirmed. The tumor suppress gene INK4a/ARF, which can translate two proteins, p16 and p14, can suppress the tumor growth via RB and P53 pathways respectively. These two proteins also supress the transplanted tumors in nude mice. DPC4 and INK4a/ARF was valuabe in experimental treatment of pancreatic carcinoma, and there potential clinical significance were noted.

结题摘要

胰腺癌危害严重、病死率高、治疗困难。为找到更好的胰腺癌分子治疗靶标,本研究从胰腺癌蛋白质组、DPC4和INK4a/ARF抑癌基因等方面进行了探讨。对12例冻存胰腺组织蛋白质组分析,从中分离鉴定出302种各种蛋白,对其蛋白组成进行了分类、统计、分析,这些结果可为胰腺疾病的研究提供参考。抑癌基因DPC4在胰腺癌中有较高的缺失率,用DPC4转染胰腺癌细胞系P2,发现DPC4基因的转染能够抑制肿瘤细胞生长(P

评估说明

    国家自然科学基金项目“DPC4抑癌基因转染胰腺癌细胞蛋白质组的改变”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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