Transcriptional regulation of hTERT promoter at GC-box and E-box region in oral cancer cell

• Main Authors: Huei Ting Yang, 楊惠婷
• Other Authors: Ann joy Chen
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/54320747359674534335

碩士 === 長庚大學 === 基礎醫學研究所 === 90 === Telomerase is a ribonucleaprotein that compose at least eight subunits including hTERT. hTERT is a catalytic subunit and is thought to play a critical role in regulation of telomerase activity. In this study, we investigate the transcriptional regulation of hTERT, especially focus on GC and E box regions of the promoter, and to examine the effect of hTERT expression on telomerase activity in oral cancer cells. First, oral cancer cell line OEC-M1 was treated with H7, a telomerase inhibitor, and the cellular status were observed. Results show that, in addition to cell cycle arrest at G2/M, telomerase activity is inhibited in dose and time course dependent manners. However, the expression of mRNA is increased in response to H7 treatment, accompanying with the decrease expression of Sp1, Sp3, USF-1 and p53 (but has no change of c-Myc). These results indicate that hTERT expression level may not correlate with telomerase activity. To clarify the role of individual transcription factor on hTERT transcriptional regulation, we co-transfect hTERT408 (core promoter) and each transcription factor one by one. Results show that Sp1 and c-Myc were able to activate hTERT, whereas Sp3, USF-1, and p53 repressed hTERT expression. We further investigated the relationship of p53 with Sp1 and Sp3. We found that p53 could inhibit Sp1 to activate hTERT expression and enhance Sp3 to repress hTERT. Besides, histone deacetylase may not involve in the p53-dependent inhibition pathway, but may involve in the process of p53 inhibiting Sp1 activation.