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

Br J Cancer. 2001 Dec 14;85(12):1914-21. doi: 10.1054/bjoc.2001.2174.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Apoptosis / physiology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Cycle
  • Cell Division
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Chloramphenicol O-Acetyltransferase / genetics
  • Clone Cells / metabolism
  • Clone Cells / transplantation
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, Reporter
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / physiology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / transplantation
  • Reactive Oxygen Species / metabolism
  • Recombinant Fusion Proteins / biosynthesis
  • Transcription Factor RelA
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tumor Cells, Cultured / transplantation

Substances

  • NF-kappa B
  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Recombinant Fusion Proteins
  • Transcription Factor RelA
  • Chloramphenicol O-Acetyltransferase