relA over-expression reduces tumorigenicity and activates apoptosis in human cancer cells.

We previously demonstrated that bcl-2 over-expression increases the malignant behaviour of the MCF7 ADR human breast cancer cell line and enhances nuclear factor-kappa B (NF-kappa B) transcriptional activity. Here, we investigated the direct effect of increased NF-kB activity on the tumorigenicity of MCF7 ADR cells by over-expressing the NF-kappa B subunit relA/p65. Surprisingly, our results demonstrated that over-expression of relA determines a considerable reduction of the tumorigenic ability in nude mice as indicated by the tumour take and the median time of tumour appearance. In vitro studies also evidenced a reduced cell proliferation and the activation of the apoptotic programme after relA over-expression. Apoptosis was associated with the production of reactive oxygen species, and the cleavage of the specific substrate Poly-ADP-ribose-polymerase. Our data indicate that there is no general role for NF-kappa B in the regulation of apoptosis and tumorigenicity. In fact, even though inhibiting NF-kappa B activity has been reported to be lethal to tumour cells, our findings clearly suggest that an over-induction of nuclear NF-kappa B activity may produce the same effect.