ERK和P38信号转导途径对慢性髓系白血病细胞周期的调控作用.docxVIP

ERK和P38信号转导途径对慢性髓系白血病细胞周期的调控作用

【摘要】本研究探讨ERK和P38信号转导途径对慢性髓系白血病细胞周期的调控作用。以RTPCR、Westernblot和FCM方法分别检测CML患者白血病细胞和K562细胞中ERK、p38、cyclinD2、cyclinE、p27的mRNA表达及蛋白表达及细胞周期分布，并分析其相关关系。结果表明：CML患者白血病细胞和K562细胞中ERK、P38、cyclinD2、cyclinE的mRNA表达和蛋白表达增高，P27的表达降低，且cyclinD2蛋白表达与cyclinE、ERK和P38蛋白表达呈正相关()，与P27蛋白表达呈负相关()。G0/G1期细胞减少，S期细胞增多，与对照组相比有显着性差异。结论：CML中P38、ERKmRNA表达和活性增加，激活下游的cyclinD2、cyclinE和P27等细胞周期调控因子，致使G0/G1期缩短，细胞快速通过G1/S转换点进入S期，加速细胞周期进程和细胞增殖，导致CML的发生。

【关键词】ERK信号转导途径P38信号转染途径；信号转导途径；慢性髓系白血病

RegulativeEffectsofERKandP38SignalTransductionPathwayonCellCycleinChronicMyeloidLeukemia

AbstractThisstudywasaimedtoinvestigatetheregulativeeffectofERKandp38signaltransductionpathwayoncellcycleofCML.ThemRNAandproteinexpressionofERK,p38,cyclinD2,cyclinEandp27(ERKandp38werePhosphERKandPhosphP38)inCMLcellsandK562celllinesweredetectedbyRTPCRandWesternblot,respectively;cellcyclewasdeterminedbyFCM,andtheirrelationshipwasanalyzed.TheresultsshowedthatthemRNAandproteinexpressionsofERK,p38,cyclinD2andcyclinEinCMLcellsandK562cellsincreased()andtheexpressionofp27decreased().TherewaspositivecorrelationbetweentheproteinexpressionsofcyclinD2andtheproteinexpreesionofERK，p38andcyclinE,buttherewasnegativecorrelationbetweentheproteinexpressionsofcyclinD2andtheproteinexpressionofp27.ThepercentageofcellsinG0/G1phasewasdecreasedandthepercentageofcellsinSphasewasincreased,therewassignificantdifferenceascomparedwithcontrol().ItisconcludedthatincreaseofthemRNAexpressionandproteinactivityofERKandp38activatethecellcycleregulatingproteinssuchascyclinD2,cyclinE,p27whichresultsinshorteningofG0/G1phase,switchingcelltoSphasethroughG1/Scheckpointquicklyandacceleratingcellcycleprogressionandcellproliferation,andeventuallyleadstooccurenceofCML.

KeywordsERKs