Early growth response-1 mediates up-regulation of telomerase in placenta.
Telomerase is thought to play a very important role in oncogenesis. It is also believed to wind back the "mitotic clock" which leads to ageing and enable permanent cell division. We evaluated telomerase activity in chorionic tissues, with particular attention to the early growth response-1 (EGR-1) gene, the importance of what was recently shown by Khachigian et al. We started our study by evaluating the relationship between activation of transcription of the human telomerase reverse transcriptase (hTERT) gene and EGR-1 gene. For this purpose, we first evaluated telomerase activity using the villous cancer cell lines JAR and JEG-3. We then demonstrated that EGR-1 plays an important role in activation of the transcription of hTERT by luciferase assay using hTERT promoter constructs. As a result of further computer analysis, we discovered a site postulated to be an EGR-1 consensus binding site at -273 to -281 in the hTERT promoter region. With forced expression of EGR-1, an increase in hTERT protein concentration was detected on Western blot analysis, while marked high expression of hTERT mRNA was observed by reverse transcriptase polymerase chain reaction. Furthermore, we evaluated the expression of EGR-1 and hTERT at the mRNA level in the placenta during the first, second and third trimesters of pregnancy and in patients with preeclampsia. Expression of EGR-1 and hTERT in the chorion increased in the first trimester of pregnancy and decreased later. Increased expression was noted in the placenta of patients with preeclampsia. The present findings suggest that EGR-1 plays an important role in activating the transcription of hTERT, showing that activation of the transcription of hTERT by EGR-1 is involved in the trophoblast growth mechanism.
Akutagawa
O
O
Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Nishi
H
H
Kyo
S
S
Higuma
C
C
Inoue
M
M
Isaka
K
K
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase