| Literature DB >> 14678994 |
Akiko Takahashi1, Fumihiro Higashino, Mariko Aoyagi, Koichi Yoshida, Miyuki Itoh, Satoru Kyo, Takatoshi Ohno, Takahiro Taira, Hiroyoshi Ariga, Kohichi Nakajima, Mitsutoki Hatta, Masanobu Kobayashi, Hidehiko Sano, Takao Kohgo, Masanobu Shindoh.
Abstract
EWS/ETS is a chimeric protein identified in most Ewing's sarcomas. Although EWS/ETS has been shown to activate transcription as a transcription factor, the detailed targets of EWS/ETS in transformed cells have not been clarified. Herein, we demonstrate that telomerase is a new target of EWS/ETS fusions. Both telomerase activity and the expression level of telomerase reverse transcriptase (TERT) mRNA were up-regulated in NIH3T3 cells transformed by EWS/E1AF and EWS/FLI1 as well as in two Ewing's sarcoma cell lines. Luciferase assay using the TERT promoter revealed that EWS/E1AF and EWS/FLI1 function as positive regulators of TERT transcription in an ETS binding site-independent manner. EWS/ETS appeared to be included in the initiation complex of TERT transcription and to cooperate with CREB-binding protein (CBP)/p300. When EWS/FLI1 was knocked down in Ewing's sarcomas cells by RNA interference, the expression level of TERT mRNA and the telomerase activity were significantly decreased. These findings indicate that EWS/ETS fusion proteins activate human telomerase activity in Ewing's tumors through up-regulation of TERT gene expression, probably as a transcriptional coactivator.Entities:
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Year: 2003 PMID： 14678994
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701