Regulation of hTERT promoter transcription activity by bHLH family genes / 中国病理生理杂志

ABSTRACT

AIM: To investigate the transcription regulation of the promoter of human telomerase reverse transcriptase (hTERT) by transcription factors c-myc and [STBX]mad1. METHODS: The various plasmids including wild type hTERT (Tw) or mutant type hTERT (Td) which both harboring luciferase gene, the expression plasmids of c-myc and [STBX]mad1, and their control vectors were constructed. The plasmids were co-trans fected into bladder cancer cell lines T24, EJ and control cells COS-7 or fibrocytes by DOTAP liposome in various combining manner, respectively. The reporter gene luciferase activities in various groups were measured 48 h after transfection. RESULTS: The luciferase activities in T24 and EJ cells treated with Tw were much higher than that in COS-7 and fibrocytes cells treated with Tw, as well as higher than that in T24 and EJ cells treated with Td, respectively. In bladder cancer T24 and EJ cells, transcription factor c-myc and [STBX]mad1 positively and negatively regulated Tw expression in a dose-dependent manner. However, the effects of c-myc and [STBX]mad1 on Td were completely opposite to Tw. Combined with c-myc and [STBX]mad1, down-regulation of Tw expression was observed. CONCLUSION: c-myc and [STBX]mad1 regulates the transcriptional activity of hTERT promoter in bladder cancer cells, and the effects might highly depend on the conservative E-box sequence CACGTG.