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.
Akutagawa
Osamu
O
Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
Nishi
Hirotaka
H
Kyo
Satoru
S
Terauchi
Fumitoshi
F
Yamazawa
Koji
K
Higuma
Chinatsu
C
Inoue
Masaki
M
Isaka
Keiichi
K
D001665:Binding Sites; D045744:Cell Line, Tumor; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D005260:Female; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*; D025721:WT1 Proteins / Q000378:metabolism
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D025721:WT1 Proteins; C509186:TERT protein, human; D019098:Telomerase