两种不同前列腺癌上皮细胞间质转化模型转录调控因子的比较及意义

Comparison of transcription factors repressing epithelial phenotype in two different prostate cancer EMT models and its significance

目的:初步筛选、对比决定两种不同前列腺癌上皮细胞间质转化(EMT)模型(LNCaP/HIF1α细胞模型、ARCaP细胞模型)表型的转录因子,为利用这两个模型深入研究前列腺癌转移机制奠定基础。方法:分别体外培养LNCaP/HIF1α细胞模型中的LNCaP细胞、稳定高表达缺氧诱导因子HIF1α的LNCaP细胞和ARCaP细胞模型中的IF11细胞、IA8细胞,提取总RNA行RT-PCR,检测目前发现的决定EMT表型的5种转录因子(Snail、Slug、ZEB1、SIP1、Twist1),对比两种模型的差异。结果:LNCaP/HIF1α细胞模型中的两种细胞均不同程度地表达5种转录因子,其中Slug、Twist1有差异,表型转化后Slug表达升高,而Twist1表达降低(P<0.05);ARCaP细胞模型中的两种细胞均不同程度地表达Snail、Slug、ZEB1、SIP1,不表达Twist1,其中ZEB1、Slug有差异,表型转化后ZEB1、Slug表达升高(P<0.05)。结论:决定不同来源的前列腺癌EMT模型表型转化的转录调控机制各不相同,Slug可能是决定HIF1α诱导LNCaP细胞EMT表型转化的关键转录因子,而ZEB1、Slug则可能在ARCaP细胞EMT表型转化中起决定作用。

Objective：To screen and compare the specific transcription factors that repress the epithelial phenotype in epithelial -mesenchymal transition（EMT） in two different human prostate cancer models LNCaP/HIF1αand ARCaP.Methods：We established two different prostate cancer EMT models,LNCaP/HIF1αand ARCaP,cultured LNCaP,LNCaP/HIF1α,IF11 and IA8 cells in vitro,and detected the five transcription factors Snail,Slug,ZEB1,SIP1 and Twist1 in these cells by RT-PCR.Results：Different levels of Snail,Slug,ZEBI,SIP1 and Twist1 were detected in both LNCaP and LNCaP/HIF1αcells,with significant differences only in the expressions of Slug and Twistl between the two cells.The expression of Slug was increased,but that of Twist1 decreased in the LNCaP/HIF1αcells.All the five transcription factors but Twist1 were expressed in both the IF11 and IA8 cells,but only the expres- sions of ZEB1 and Slug were increased significantly in the IA8 cells.Conclusion：There are different mechanisms underlying transcriptional regulation in different prostate cancer EMT models.Slug may be one of the key transcription factors involved in the HIF1α-induced EMT of LNCaP cells,while ZEB1 and Slug may play an important role in repressing the epithelial phenotype of the ARCaP model.