全反式维甲酸诱导下NB4细胞TGF-β1信号转导途径基因表达的变化  

The mRNA expressions in TGF-β1 signaling transduction pathways during the differentiation of NB4 cells induced by ATRA

作　　者：徐榕[1] 陈芳源[1] 钟华[1] 赵劲秋[1] 黄洪晖[1] 林佳瑶[1] 欧阳仁荣[1] 

机构地区：[1]上海交通大学医学院附属仁济医院血液科,上海200127

出　　处：《肿瘤》2008年第10期847-851,共5页Tumor

基　　金：上海市科委基金资助项目(编号:04ZR14106)

摘　　要：目的:探讨全反式维甲酸(all-transretinoic acid,ATRA)诱导分化急性早幼粒细胞白血病(acute promyelocytic leuke-mia,APL)过程中转化生长因子(transforming growth factor-β1,TGF-β1)信号转导途径基因表达的变化。方法:应用荧光实时定量PCR(real-time fluorogentic quantitative PCR,RFQ-PCR)的方法检测ATRA作用于人APL细胞株NB4不同时间后TGF-β1、TGF-βRⅠ、TGF-βRⅡ、Smad2、Smad3、Smad4和Smad7 mRNA表达的变化。利用共聚焦显微镜观察NB4细胞中间接免疫荧光法标记的PML-RARα融合蛋白和Smad3蛋白定位。结果:在ATRA诱导NB4细胞分化过程中,TGF-β1、TGF-βRⅠ、TGF-βRⅡ、Smad 2、Smad 3、Smad 4和Smad 7的表达量逐渐上升,48或72h时表达量达到最高,然后逐渐下降,而无水乙醇对照组则无明显变化;在NB4细胞中PML-RARα融合蛋白和Smad3蛋白有共定位现象。结论:TGF-β1信号转导途径与NB4细胞的分化密切相关,ATRA可以上调该信号转导途径中基因的表达。PML-RARα融合蛋白可以和Smad3蛋白结合。Objective：To study the mRNA expression in TGF-β1 signaling transduction pathways during the differentiation of acute promyelocytic leukemia （APL） induced by all-transretinoic acid （ATRA）. Methods：The mRNA expressions of TGF-β1, TGF- βR I , TGF-βR Ⅱ , Smad 2, Smad 3, Smad 4, and Smad 7 of human APL cell line NB4 were analyzed using a real-time fluorogentic quantitative-polymerase chain reaction （RFQ-PCR） assay after treatment with ATRA. The locations of PML-RARct fusion protein and Smad3 protein in NB4 cells were determined by eonfoeal microscopy. Results：The mRNA expression levels of TGF-β1 , TGF-βR I , TGF-βRⅡ , Smad 2, Smad 3, Smad 4, and Smad 7 increased gradually during the NB4 cells＇ differentiation induced by ATRA. Their expression reached the peak at 48 h or 72 h and then declined gradually. But there was no significant difference in the dehydrated alcohol-treated group （control）. PML-RARα fusion protein and Smad 3 protein were co-localized in NB4 cells. Conclusion： TGF-β1 signaling transduction pathways are closely related with NB4 cells＇ differentiation. ATRA can up-regulate the mRNA expression levels involved in the signaling transduction pathway. PML-RARα fusion protein is apt to bind with Smad 3 protein.

关 键 词：白血病 粒细胞 急性 维甲酸 基因表达调控 白血病 

分 类 号：R733.7[医药卫生—肿瘤]