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
