干细胞因子和缺氧诱导因子1α在胰腺癌细胞的表达和机制  

Expressions of stem cell factor and hypoxia inducible factor 1 alpha in pancreatic cancer cells and related mechanism

作　　者：张珉 王云检 李琼[2] 李庆军 杨楠木 尤国华 王莉 

机构地区：[1]郑州大学附属肿瘤医院肝胆外科,河南郑州450000 [2]新乡医学院,河南新乡453000

出　　处：《细胞与分子免疫学杂志》2017年第7期920-925,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金联合基金(U1404820);河南省重点科技攻关项目(142102310438)

摘　　要：目的研究干细胞因子(SCF)和缺氧诱导因子1α(HIF-1α)在胰腺癌中表达的相关性,并探讨SCF对HIF-1α表达的调控机制。方法使用免疫组织化学染色检测胰腺癌标本SCF和HIF-1α的表达,分析两种分子表达的相关性。用(0、1、10、100)ng/m L SCF和5μmol/L c-KIT抑制剂格列卫(Gleevec)单独或联合处理胰腺癌PANC-1细胞,实时荧光定量PCR检测HIF-1αmRNA水平,Western blot法检测HIF-1α蛋白水平、胞外信号调节激酶1/2(ERK1/2)、AKT磷酸化水平。结果胰腺癌组织SCF和HIF-1α的表达上调,二者表达呈正相关。在PANC-1细胞中,SCF不能影响HIF-1α的mRNA表达,但能够上调HIF-1α的蛋白表达,且呈浓度依赖性。Gleevec不能影响HIF-1α的mRNA表达,但能够抑制SCF对HIF-1α蛋白的上调作用,下调ERK1/2、AKT的磷酸化水平。结论 SCF/c-KIT可激活胰腺癌PANC-1细胞AKT和ERK信号通路上调HIF-1α蛋白表达。Objective To study the correlation between the expressions of stem cell factor（ SCF） and hypoxia inducible factor 1 alpha（ HIF-1α） in pancreatic cancer,and investigate the mechanism by which SCF regulates the expression of HIF-1α.Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF（ 0,1,10,100 ng/m L） alone or combined with c-KIT inhibitor Gleevec（ 5 μmol/L）. Real-time fluorescent quantitative PCR（ qRT-PCR） was performed to detect the level of HIF-1α mRNA,and Western blotting to detect the HIF-1αprotein level,the phosphorylation levels of ERK1/2 and AKT. Results SCF and HIF-1α were up-regulated in pancreatic cancer samples and they had an obvious positive correlation. In PANC-1 cells,SCF didn＇t affect the expression of HIF-1αmRNA,but up-regulated the expression of HIF-1α protein in a dose-dependent manner. Gleevec inhibited the SCF-induced up-regulation of HIF-1α protein,but did not affect the mRNA. And Gleevec blocked the phosphorylation of AKT and ERK1/2.Conclusion SCF/c-KIT can up-regulate the protein expression of HIF-1α by activating AKT and ERK signaling pathways in pancreatic cancer cells.

关 键 词：胰腺癌 干细胞因子(SCF) 缺氧诱导因子1α(HIF-1α) 格列卫(Gleevec) 

分 类 号：R735.9[医药卫生—肿瘤] Q279[医药卫生—临床医学]