CAJ | 학술논문

目的:探讨BCR/ABL融合基因对抑癌基因P7芑_Ⅳ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、10 μg/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、72 h)后,通过荧光定量PCR检测细胞BCR/ABL、FIEN、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FIEN mRNA表达的影响.结果:1 μg/ml格列卫作用K562细胞后随着BCR/ABL融合基因表达减低,FIEN 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,FIEN 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.
목적:탐토BCR/ABL융합기인대억암기인P7기_Ⅳ개도적신호전도통로재K562세포증식화조망중적영향.방법:용불동농도적격렬위(0.5、1、2、5、10 μg/ml)간예K562세포불동시간,관찰기대세포증식적영향.용1μg/ml농도적격렬위간예K562세포불동시간(12、24、36、48、72 h)후,통과형광정량PCR검측세포BCR/ABL、FIEN、mTOR mRNA수평적변화,병분석타문지간적상호관계.Western blotting검측세포Akt화p-Akt수평,분석BCR/ABL융합기인대FIEN mRNA표체적영향.결과:1 μg/ml격렬위작용K562세포후수착BCR/ABL융합기인표체감저,FIEN mRNA표체상조,mTOR mRNA표체하조,p-Akt표체하조.48h후수착BCR/ABL융합기인적억제감약,FIEN mRNA표체진이감저,이mTOR mRNA표체승고,p-Akt지속강저.BCR/ABL mRNA표체여PTEN mRNA표체정부상관(r=-0.881,P<0.05),여mTOR mRNA급p-Akt표체정정상관(의차위r=0.961,r=0.879,P균<0.05).결론:BCR/ABL융합기인가이통과억제PTEN기인표체,조공PI3K/Akt、mTOR신호전도통로,삼여세포증식、조망급세포주기조공등생물학특성.
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 FIEN 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 FTEN 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 FIEN mRNA showed a positive correlation; whilst BCR/ABL had a negative correlation with mTOR mRNA and p-Akt protein. CONCLUSION: BCR/ABL fusion gene could regulate p-Akt, mTOR pathway by inhibiting PIEN expression in K562 cells and affected cell proliferation, apoptosis and cell cycle.