Keywords :
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
Abstract :
[en] 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.
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