BCR/ABL基因对PTEN介导的信号通路在K562细胞增殖和凋亡中的影响  

Effects of BCR/ABL fusion gene on PTEN signaling pathway in proliferation and apoptosis of K562 cells

作　　者：梁文同[1] 成志勇[1] 牛志云[2] 刘慧光 颜晓燕[1] 于琳艳 

机构地区：[1]保定市第一医院血液内科,河北保定071000 [2]河北医科大学第二医院血液内科,河北石家庄050000 [3]高阳县医院内科,河北高阳071500

出　　处：《癌变．畸变．突变》2010年第1期6-9,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：河北省科技攻关计划项目(072761130)

摘　　要：目的:探讨BCR/ABL融合基因对抑癌基因PTEN介导的信号传导通路在K562细胞增殖和凋亡中的影响。方法:用不同浓度的格列卫(0.5、1、2、5、10μg/ml)干预K562细胞不同时间,观察其对细胞增殖的影响。用1μg/ml浓度的格列卫干预K562细胞不同时间(12、24、36、48、72h)后,通过荧光定量PCR检测细胞BCR/ABL、PTEN、mTOR mRNA水平的变化,并分析它们之间的相互关系。Western blotting检测细胞Akt和p_Akt水平,分析BCR/ABL融合基因对PTEN mRNA表达的影响。结果:1μg/ml格列卫作用K562细胞后随着BCR/ABL融合基因表达减低,PTEN mRNA表达上调,mTOR mRNA表达下调,p_Akt表达下调。48h后随着BCR/ABL融合基因的抑制减弱,PTEN mRNA表达进而减低,而mTOR mRNA表达升高,p_Akt持续降低。BCR/ABL mRNA表达与PTEN mRNA表达呈负相关(r=-0.881,P<0.05),与mTOR mRNA及p_Akt表达呈正相关(依次为r=0.961,r=0.879,P均<0.05)。结论:BCR/ABL融合基因可以通过抑制PTEN基因表达,调控PI3K/Akt、mTOR信号传导通路,参与细胞增殖、凋亡及细胞周期调控等生物学特性。OBJECTIVE： To investigate the regulatory mechanism of oncogene BCR/ABL fusion gene on PTEN signaling pathway in proliferation and apoptosis of K562 cells in vitro. METHODS： To detect the mRNA levels of BCR/ABL, PTEN and mTOR in K562 cells treated with different concentrations of Imatinib by real-time fluorescent relative-quantification reverse transcriptional PCR （FQ-PCR） and the protein levels of Akt, p-Akt by Western blotting technique. RESULTS： The expression level of PTEN mRNA was up-regulated and the mTOR mRNA was down-regulated with the reduction of BCR/ ABL fusion gene in the initial 36 h after 1 μg/ml imatinib inhibiting K562 cells. Then the PTEN mRNA decreased and the mTOR mRNA expression restored, but the p-Akt was continuously down-regulated with the restoration of BCR/ABL fusion gene 48 h later. BCR/ABL and PTEN mRNA showed a positive correlation; whilst BCR/ABL had a negative correlation with roTOR mRNA and p-Akt protein. CONCLUSION： BCR/ABL fusion gene could regulate p-Akt, mTOR pathway by inhibiting PTEN expression in K562 cells and affected cell proliferation, apoptosis and cell cycle.

关 键 词：BCR/ABL融合基因 PTEN MTOR AKT 

分 类 号：R733[医药卫生—肿瘤]