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目的探讨转录因子E2F-1(E2F transcription factor 1)对c-Myc诱导端粒酶逆转录酶(human telomerasereverse transcriptase,hTERT)表达的负反馈调控作用。方法以人胚胎成纤维细胞为实验模型,采用基因转染、基因表达抑制实验等探讨E2F-1对c-Myc诱导hTERT表达及下游信号通路的影响。结果 c-Myc激活可同时诱导E2F-1和hTERT的表达,不同的是,仅在c-Myc高度激活时E2F-1表达水平有显著提高,而hTERT表达则呈现一定的剂量依赖性;在c-Myc高度激活时,E2F-1蛋白表达水平显著提高,并致细胞凋亡比率增加;在c-Myc中低度激活时,抑制E2F-1表达,可致hTERT活化水平上升,而在c-Myc高度激活时抑制E2F-1表达,可避免细胞进入凋亡程序,且细胞端粒酶活性有进一步增加。结论在正常细胞中,E2F-1对c-Myc诱导hTERT表达具有负反馈调节作用,对限制癌基因c-Myc的信号转导有重要意义。
Objective To investigate the negative feedback regulation of transcription factor E2F-1 (E2F transcription factor 1) on c-Myc-induced telomerase reverse transcriptase (hTERT) expression. Methods Human embryonic fibroblasts were used as experimental models to investigate the effect of E2F-1 on c-Myc-induced hTERT expression and downstream signaling pathway by gene transfection and gene expression inhibition experiments. Results Activation of c-Myc induced the expression of E2F-1 and hTERT at the same time, except that the expression of E2F-1 was significantly increased only when c-Myc was highly activated and the expression of hTERT was dose-dependent. In c -Myc is highly activated, the expression of E2F-1 protein is significantly increased, and the rate of apoptosis is increased; in the low activation of c-Myc, the inhibition of E2F-1 expression can increase the activation of hTERT, while in c- Inhibition of E2F-1 expression by Myc hyperactivity prevents cells from entering the apoptotic program and further increases telomerase activity. Conclusion In normal cells, E2F-1 has a negative feedback regulation on c-Myc-induced hTERT expression, which is of great significance for limiting the signal transduction of c-Myc oncogene.