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

Cancer Sci. 2008 Jul;99(7):1401-6. doi: 10.1111/j.1349-7006.2008.00835.x. Epub 2008 May 2.

Abstract

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.

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Down-Regulation
  • Early Growth Response Protein 1 / physiology*
  • Female
  • Humans
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Telomerase / antagonists & inhibitors
  • Telomerase / genetics*
  • Uterine Cervical Neoplasms / enzymology*
  • WT1 Proteins / metabolism

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • RNA, Messenger
  • WT1 Proteins
  • TERT protein, human
  • Telomerase