Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells.
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.
Deregowski
Valérie
V
Laboratories of Clinical Chemistry and Human Genetics, Center for Molecular and Cellular Therapy, University of Liège, Liège, Belgium.
Delhalle
Sylvie
S
Benoit
Valérie
V
Bours
Vincent
V
Merville
Marie-Paule
MP
D001943:Breast Neoplasms / Q000473:pathology; D051242:Caveolin 1; D022461:Caveolins / Q000032:analysis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D036382:Ephrin-A1; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000473:pathology; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D016207:Cytokines; D036382:Ephrin-A1; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger