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  • Oncogenomics
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Identification of NF-κB-regulated genes induced by TNFα utilizing expression profiling and RNA interference

Oncogene volume 22, pages 2054–2064 (2003)Cite this article

A Corrigendum to this article was published on 16 December 2004

Abstract

Tumor necrosis factor α (TNFα) is a proinflammatory cytokine with important roles in regulating inflammatory responses as well as cell cycle proliferation and apoptosis. Although TNFα stimulates apoptosis, it also activates the transcription factor NF-κB, and studies have shown that inhibition of NF-κB potentiates the cytotoxicity of TNFα. Since several chemotherapy agents act like TNFα to both promote apoptosis and activate NF-κB, understanding the role of NF-κB in suppressing apoptosis may have significant clinical applications. To understand the effects of stimulation with TNFα and the role of NF-κB in regulating this response, a 23k human cDNA microarray was used to screen TNFα-inducible genes in HeLa cells. Real-time PCR verified expression changes in 16 of these genes and revealed three distinct temporal patterns of expression after TNFα stimulation. Using RNA interference to disrupt expression of the p65 subunit of NF-κB, all but two of the genes were shown to depend on this transcription factor for their expression, which correlated well with the existence of NF-κB binding sites in most of their promoters. Inflammatory, proapoptotic, and antiapoptotic genes were all shown to be regulated by NF-κB, demonstrating the wide variety of targets activated by NF-κB signaling and the necessity of differentiating among these genes for therapeutic purposes.

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Acknowledgements

We like to thank Dr Rama M Surabhi for the development of the p65 siRNA oligonucleotides, Denise Tavana for growing the HeLa cells, Udit Verma for helpful suggestions, and Alejandra Herrera for help with preparation of the figures. This work was supported by The Harold Simmons Cancer Center, The Grant Dove Foundation, The National Women's Cancer Research Alliance, and NIH grant CA74128.

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  1. Richard B Gaynor

    Present address: Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46285, USA

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390-8594, TX, USA

    Anwu Zhou, Shane Scoggin, Richard B Gaynor & Noelle Sevilir Williams

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  1. Anwu Zhou
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  2. Shane Scoggin
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Correspondence to Noelle Sevilir Williams.

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Zhou, A., Scoggin, S., Gaynor, R. et al. Identification of NF-κB-regulated genes induced by TNFα utilizing expression profiling and RNA interference. Oncogene 22, 2054–2064 (2003). https://doi.org/10.1038/sj.onc.1206262

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