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KMID : 1140120050100040211
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Cancer Prevention Research
2005 Volume.10 No. 4 p.211 ~ p.216
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The Synergistic Role of c-Myc in Transactivation of hTERT of Cancer Cell
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Kim Yong-Seok
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Abstract
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Human telomerase catalytic subunit (hTERT), as a component of telomerase was identified as a determining factor of telomerase activity. Telomerase, as a ribonucleoprotein polymerase, maintains telomere length. Telomere length is a molecular clock determining cellular fate toward apoptosis, senescence or immortalization. In normal human somatic cells, telomere length is not maintained because telomerase is not active except sperm and stem cells. However, in most cancer cells, telomerase becomes active, and telomerase, as a key factor for telomere length has been studied to investigate its control mechanism. This study was focused on the role of c-Myc as the possible factors involved in transcriptional control of hTERT. C-Myc has several binding sites on hTERT promoter and stimulated hTERT promoter activity by its overexpression. However, hTERT promoter activity was not stimulated by regular expression of c-Myc. C-Myc inhibited the transactivation of hTERT promoter by ERT, ETS2, and p53. Also, c-Myc showed synergistic activation of hTERT promoter with ESE-2 and ESE-3. Especially, the degree of transactivation of hTERT promoter by ESE-3 was increased upto 79.8 fold by the synergistic role of c-Myc. Therfore, hTERT seemed to be transcriptionally regulated by synergistic action of some specific factors and regularly expressed factors like c-Myc and SP1 which have binding sites on hTERT promoter of cancer cell.
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KEYWORD
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hTERT, Telomerase, c-Myc, ESE-3, Synergistic action
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