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

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.

• Authors: Valérie Deregowski, Sylvie Delhalle, Valérie Benoit, Vincent Bours, Marie-Paule Merville
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 64 Issue 5-6 Pg. 873-81 (Sep 2002) ISSN: 0006-2952 [Print] England
• PMID: 12213581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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