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.
Ricca
A
A
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
Biroccio
A
A
Trisciuoglio
D
D
Cippitelli
M
M
Zupi
G
G
Del Bufalo
D
D
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism / Q000637:transplantation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000637:transplantation
D016328:NF-kappa B; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D015500:Chloramphenicol O-Acetyltransferase