Early growth response-1 mediates downregulation of telomerase in cervical cancer
Early growth response-1 mediates downregulation of telomerase in cervical cancer
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DOI：
10.1111/j.1349-7006.2008.00835.x
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发表时间：
2008-07-01
期刊：
影响因子：
5.7
通讯作者：
Isaka, Keiichi
中科院分区：
文献类型：
--
作者：
Akutagawa, Osamu;Nishi, Hirotaka;Isaka, Keiichi
早期生长反应（Egr）-1是一种转录因子，在各种刺激的15 - 30分钟内触发下游基因的转录。这些基因通过特异性启动子激活快速表达，并介导细胞生长和血管生成。在此基础上，本研究探讨了Egr-1在宫颈癌组织中对端粒酶逆转录酶（hTERT）和端粒酶的调控作用。首先，在mRNA水平上检测宫颈癌组织中Egr-1和hTERT的表达。Egr-1和hTERT在宫颈癌组织中的表达明显高于正常宫颈组织。Egr-1与hTERT表达呈负相关。通过使用hTERT启动子构建体的荧光素酶测定，当Egr-1过表达时，hTERT转录激活被抑制。此外，Egr-1过表达减少hTERT蛋白质的生产以及hTERTmRNA的观察，通过Western印迹分析和实时逆转录聚合酶链反应，分别。本研究表明Egr-1在hTERT的转录激活中起重要的调节作用。
Early growth response (Egr)-1 is a transcription factor that triggers transcription of downstream genes within 15 - 30 min of various stimulations. These genes are expressed rapidly through specific promoter activation and mediate cell growth and angiogenesis. Following the previous computational identification of a site that was thought to be an Egr-1 consensus binding site at - 273 to - 281 in the human telomerase reverse transcriptase (hTERT) promoter region, the present study was conducted to evaluate the role of Egr-1 in the regulation of hTERT and telomerase in uterine cervical cancer. First, the expression of Egr-1 and hTERT at the mRNA level was examined in cervical cancer tissues. Egr-1 and hTERT were expressed much higher in cervical cancer tissues than in the normal cervix. However, a negative correlation was noted in the expression between Egr-1 and hTERT. By luciferase assay using hTERT promoter constructs, hTERT transcriptional activation was shown to be inhibited when Egr-1 was overexpressed. Furthermore, Egr-1 overexpression decreased hTERT protein production as well as hTERT mRNA as observed by western blotting analysis and real-time reverse transcription-polymerase chain reaction, respectively. The present study suggests that Egr-1 plays an important regulatory role in the transcriptional activation of hTERT.