Expression of transcription factor Sp1 in hepatocellular carcinoma
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摘要:
目的通过研究转录因子Sp1在肝细胞癌(HCC)组织中的表达及转化生长因子(TGF)β1对肝癌细胞中Sp1 mRNA转录表达的影响,探讨Sp1在HCC中表达的意义及其在细胞凋亡中的作用。方法免疫组织化学方法对51例HCC组织与10例良性病变而切除的正常肝组织中转录因子Sp1进行蛋白检测;体外培养肝癌细胞株HepG2,施加外源性TGFβ1,逆转录-聚合酶链反应方法检测HepG2细胞中Sp1 mRNA的表达,并用流式细胞仪检测细胞受到干预后的凋亡情况。结果 Sp1蛋白在HCC组织中的表达率明显高于正常肝组织(P<0.01);施加外源性TGFβ1与对照组相比HepG2细胞Sp1mRNA的表达显著降低(P<0.01),且HepG2细胞凋亡率随着TGFβ1浓度的增高而上升。结论 Sp1蛋白在HCC中的过表达在肿瘤发生发展中起一定作用;TGFβ1诱导肝癌细胞凋亡,而Sp1基因的抑制在TGFβ1诱导肝癌细胞凋亡中可能起一定作用。
Abstract:Objective To determine whether the transcription factor Sp1 is differentially expressed in human hepatocellular carcinoma (HCC) and to investigate the potential pro-apoptotic effect of transforming growth factor beta 1 (TGFβ1) through Sp1 by using the HCC cell line HepG2.Methods The Sp1 expression patterns were detected by immunohistochemistry in tumors from 51 cases of HCC and 10 specimens of normal liver tissues.HepG2 cells in culture were stimulated by TGFβ1 and the change in Sp1 mRNA expression was detected by RT-PCR while the change in cell apoptosis rate was detected by flow cytometry.Statistical significance of changes were assessed by one-way ANOVA.Results The positive rate of Sp1 expression was significantly higher in HCC tissue than in normal liver tissues (P<0.01) .The level of Sp1 mRNA was significantly lower in HepG2 cells stimulated with TGFβ1 than in the control cells (P<0.01) , and the effect was TGFβ1 dose-dependent.The apoptosis rate of HepG2 cells increased in correspondence with increases in TGFβ1 concentration.Conclusion Overexpression of Sp1 may functionally contribute to HCC occurrence and development.TGFβ1 can induce apoptosis of HepG2 HCC cells in vitro, and this apoptotic effect may involve Sp1.
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Key words:
- transforming growth factor beta 1 /
- Sp1 transcription factor /
- carcinoma /
- hepatocellular
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