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  • Original Paper
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Increased and correlated nuclear factor-kappa B and Ku autoantigen activities are associated with development of multidrug resistance

Oncogene volume 20, pages 6048–6056 (2001)Cite this article

Abstract

In this study, we investigated possible engagement of NF-κB and Ku autoantigen (Ku) activation in development of multidrug resistance (MDR) and circumvention of MDR by modulation of NF-κB and Ku. The NF-κB activity and NF-κB p65 subunit level were constitutively higher in MDR cells than in drug-sensitive parental cells. Interestingly, a faster running NF-κB DNA binding complex was identified as Ku, a DNA damage sensor and a key double strand break repair protein, and was positively correlated with the NF-κB activity in MDR cells and Ku- or both subunits of NF-κB-transfected cells. Also both NF-κB and Ku activities were activated or inhibited by treatment with etoposide (VP-16) or MG-132 (a proteasome inhibitor), respectively. Furthermore, PKA inhibitor suppressed markedly the constitutive and drug-induced activities of NF-κB and Ku in MDR cells and subsequently potentiated the cytotoxic activity of anticancer drugs. Our results proposed that the NF-κB and Ku activation could be one of multi-factorial MDR mechanism, and PKA inhibitor, likely via inhibition of NF-κB and Ku activities, could enhance the effectiveness of anticancer drugs against MDR cells with high activities of NF-κB and Ku.

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Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea. (HMP-00-B-20900-0089)

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Author notes

  1. Jee Hyun Um and Chi Dug Kang: JH Um and CD Kang equally contributed to this work

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Pusan National University, Pusan, 602-739, South Korea

    Jee Hyun Um, Chi Dug Kang, Bok Gun Lee, Byung Seon Chung & Sun Hee Kim

  2. Research Center for Molecular Medicine, College of Medicine, Pusan National University, Pusan, 602-739, South Korea

    Jee Hyun Um & Chi Dug Kang

  3. Department of Microbiology, College of Natural Sciences, Chang Won National University, Chang Won, 641-773, South Korea

    Dong Wan Kim

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  1. Jee Hyun Um
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Correspondence to Sun Hee Kim.

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Um, J., Kang, C., Lee, B. et al. Increased and correlated nuclear factor-kappa B and Ku autoantigen activities are associated with development of multidrug resistance. Oncogene 20, 6048–6056 (2001). https://doi.org/10.1038/sj.onc.1204732

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