Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells

Biochem Pharmacol. 2002 Sep;64(5-6):873-81. doi: 10.1016/s0006-2952(02)01151-6.

Abstract

NF-kappaB is a pleiotropic transcription factor controlling the expression of many genes and viruses. NF-kappaB plays a role in immune response, cellular adhesion or acute phase response. It also inhibits apoptosis and favors cancer cell survival. We studied the expression of genes controlled by NF-kappaB in ovarian and breast adenocarcinoma cancer cells. We stably transfected OVCAR-3 and MCF7 A/Z cells with an expression vector coding for the mutated inhibitor IkappaBalpha, which sequesters NF-kappaB in the cytoplasm. We stimulated control and IkappaBalpha expressing cells with IL-1beta or TNF-alpha and extracted the RNA, which was reverse-transcribed and hybridized to DNA microarrays. Several of the genes identified were not known as NF-kappaB target genes. Among them, we confirmed the differential expression of ephrin-A1 and caveolin-1 by quantitative real-time polymerase chain reaction. Our results showed an NF-kappaB-dependent induction of ephrin-A1 and caveolin-1 mRNAs after stimulation with TNF-alpha and IL-1beta, confirming that NF-kappaB controls target genes implied in tumor angiogenesis and cell transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / pathology
  • Caveolin 1
  • Caveolins / analysis*
  • Caveolins / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cytokines / metabolism*
  • Ephrin-A1
  • Female
  • Gene Expression Profiling
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / pathology
  • Proteins / analysis*
  • Proteins / genetics
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • CAV1 protein, human
  • Caveolin 1
  • Caveolins
  • Cytokines
  • Ephrin-A1
  • NF-kappa B
  • Proteins
  • RNA, Messenger