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Inhibition of the NF-kappa B transcription factor increases Bax expression in cancer cell lines.

par Bentires-Alj, M;Dejardin, Emmanuel;Viatour, Patrick;Van Lint, Carine ;Froesch, B;Reed, J C;Merville, Marie-Paule;Bours, Vincent
Référence Oncogene, 20, 22, page (2805-2813)
Publication Publié, 2001

Article révisé par les pairs

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Résumé :

The NF-kappa B transcription factor has been shown to inhibit apoptosis in several experimental systems. We therefore investigated whether the expression of the Bax proapoptotic protein could be influenced by NF-kappa B activity. Increased Bax protein expression was detected in HCT116, OVCAR-3 and MCF7 cells stably expressing a mutated unresponsive I kappa B-alpha inhibitory protein that blocks NF-kappa B activity. Northern blots showed that bax mRNA expression was increased as a consequence of mutated I kappa B-alpha expression in HCT116 cells. A careful examination of the human bax gene promoter sequence showed three putative binding sites for NF-kappa B, and the kappa B2 site at position -687 could indeed bind NF-kappa B complexes in vitro. Transient transfection of a bax promoter luciferase construct in HCT116 cells showed that NF-kappa B proteins could partially inhibit the transactivation of the bax promoter by p53. Mutations or deletions of the kappa B sites, including kappa B2, indicated that this NF-kappa B-dependent inhibitory effect did not require NF-kappa B DNA-binding, and was thus an indirect effect. However, cotransfection of expression vectors for several known cofactors failed to identify a competition between p53 and NF-kappa B for a transcription coactivator. Our findings thus demonstrate for the first time that NF-kappa B regulates, through an indirect pathway, the bax gene expression.