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Early growth response‐1 mediates downregulation of telomerase in cervical cancer

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. (Cancer Sci 2008; 99: 1401–1406)