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

Abstract

NF-κB is a pleiotropic transcription factor controlling the expression of many genes and viruses. NF-κB 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-κB 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 IκBα, which sequesters NF-κB in the cytoplasm. We stimulated control and IκBα expressing cells with IL-1β or TNF-α and extracted the RNA, which was reverse-transcribed and hybridized to DNA microarrays. Several of the genes identified were not known as NF-κB 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-κB-dependent induction of ephrin-A1 and caveolin-1 mRNAs after stimulation with TNF-α and IL-1β, confirming that NF-κB controls target genes implied in tumor angiogenesis and cell transformation.