Transfer of E2F-1 to human glioma cells results in transcriptional up-regulation of Bcl-2.
Cancer Res
; 61(18): 6693-7, 2001 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-11559537
ABSTRACT
Strong evidence exists to support the tenet that activation of E2F transcription factors, via alterations in the p16-cyclin D-Rb pathway, is a key event in the malignant progression of most human malignant gliomas. The oncogenic ability of E2F has been related to the E2F-mediated up-regulation of several proteins that positively regulate cell proliferation. However, E2F may indirectly enhance proliferation by activating antiapoptotic molecules. In this work, we sought to ascertain whether E2F-1-mediated events involve the up-regulation of the antiapoptotic molecule Bcl-2. Western blot analyses showed up-regulation of Bcl-2 but not of Bcl-x(L) by 24 h after the transfer of E2F-1. Northern blot studies showed that transfer of E2F-1 also up-regulated Bcl-2 RNA. In support of these findings and the concept that E2F-1 has a direct effect in the induction of Bcl-2, we found a putative E2F binding site within the Bcl-2 sequence. Subsequent gel-mobility shift and supershift experiments involving the CTCCGCGC site in the bcl-2 promoter showed that E2F-1 bound Bcl-2. Transactivation experiments consistently showed that ectopic E2F-1 activated responsive elements located in the -1448/-1441 region in the P1 promoter region of the bcl-2 gene. As expected, other members of the E2F family of transcription factors such as E2F-2 and E2F-4 also transactivated the bcl-2 promoter. Our results demonstrate that E2F-1 modulates the expression of the antiapoptotic molecule Bcl-2 and suggest that up-regulation of Bcl-2 may favor the oncogenic role of E2F-1 and other members of the E2F family of transcription factors.
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Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Activación Transcripcional
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Proteínas de Ciclo Celular
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Proteínas Proto-Oncogénicas c-bcl-2
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Proteínas de Unión al ADN
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Glioma
Límite:
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos