胰腺癌上调因子在胰腺癌发病及药物治疗中的作用高崇崇刘殿刚曹峰.docVIP

胰腺癌上调因子在胰腺癌发病及药物治疗中的作用 高崇崇 刘殿刚 曹峰 李非* DOI:10.3760/cma.j.issn.1007-8118.2014.00.000 基金项目：国家自然科学基金 作者单位：100053 首都医科大学宣武医院普外科 通信作者：李非，电子信箱：feili36@ccmu.edu. [摘要] 胰腺癌上调因子(PAUF)是新近发现的癌基因，其在胰腺癌高表达，能够通过激活CXCR4、β-catenin 、TPL2/MEK/ERK 、FAK/Scr等信号通路、增加胰腺癌细胞间的黏附性、促进胰腺癌血管生成及增加血管通透性等方式来促进胰腺癌迁徙、转移及进展。同时这些信号通路与吉西他滨耐药密切相关。因此我们推测PAUF亦参与调节吉西他滨对胰腺癌细胞的耐药，目前国内外尚缺乏PAUF调节胰腺癌细胞吉西他滨耐药及其机制方面的研究。因此对其进行深入研究有利于明确胰腺癌化疗耐药机制及为胰腺癌治疗提供新的靶点。 [关键词] 胰腺癌上调因子;胰腺癌;信号通路;吉西他滨 Research advances of the new oncogene PAUF in pancreatic cancer pathogenesis and treatment Gao Chong-chong， Liu Dian-gang，Cao Feng ，Li Fei*. Department of General Surgery，Xuanwu Hospital，Capital University of Medical Sciences，Beijing 100053，P．R．China Corresponding author：Li Fei，Email：feili36@ccmu.edu. cn [Abstract] Pancreatic adenocarcinoma up-regulated factor(PAUF), a newly disc- overed gene, is highly expressed in pancreatic cancer. PAUF promotes the metastasis and progression of pancreatic cancer through many ways, such as the activation of signal pathway (CXCR4、β-catenin 、TPL2/MEK/ERK 、FAK/Scr),increasing the adhesive- ness of pancreatic cancer cells, promoting angiogenesis and vascular permeability. Simultaneously, CXCR4、β-catenin 、TPL2/MEK/ERK and FAK/Scr are closely related with gemcitabine-resistance. Based on this theory, we infer that PAUF plays a role in gemcitabine-resistance of pancreatic cancer cells. So far, no related research has been done domestic and overseas . The research may find a clue for the mechanism of chemotherapy- resistance and provide a new target spot for the therapy of pancreatic cancer. [Key words] PAUF；pancreatic cancer；signal pathway； gemcitabine 胰腺癌是一种恶性程度极高的消化系统肿瘤，具有发现晚，转移早，进展快，预后差等特点。一旦确诊，其存活期仅为2-8个月，而5 年生存率仅有1%～4％ ADDIN NE.Ref.{9CFE0845-54F5-4CA5-8E29-C5CB4DBA8494}[1-2] 。手术切除是可能根治的唯一方法。然而，由于目前尚缺乏早期诊断手段，70％～80％患者确诊时已经出现局部侵犯和（或）远处转移而失去手术时机[3]。即使可以接受根治手术的患者其术后5 年生存率也只有20％ ADDIN NE.Ref.{84B18E4B-5282-4232-A750-3E8827A1E5CE}[4]。胰腺癌对现有的其它治疗手段如放化疗等不敏感 ADDIN NE.Ref.{84B18E4