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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Mitochondrial dysfunction suppresses p53 expression via calcium-mediated nuclear factor-κB signaling in HCT116 human colorectal carcinoma cells

  • Lee, Young-Kyoung (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Yi, Eui-Yeun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, Shi-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jang, Won-Jun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Han, Yu-Seon (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Jegal, Myeong-Eun (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, Yung-Jin (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • Received : 2017.12.07
  • Accepted : 2018.03.05
  • Published : 2018.06.30
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Abstract

Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types. Although the correlation between mitochondrial dysfunction and cancer malignancy has been demonstrated by several studies, further research is required to elucidate the molecular mechanisms underlying accelerated tumor development and progression due to mitochondrial mutations. We generated an mtDNA-depleted cell line, ${\rho}^0$, via long-term ethidium bromide treatment to define the molecular mechanisms of tumor malignancy induced by mitochondrial dysfunction. Mitochondrial dysfunction in ${\rho}^0$ cells reduced drug-induced cell death and decreased the expression of pro-apoptotic proteins including p53. The p53 expression was reduced by activation of nuclear $factor-{\kappa}B$ that depended on elevated levels of free calcium in $HCT116/{\rho}^0$ cells. Overall, these data provide a novel mechanism for tumor development and drug resistance due to mitochondrial dysfunction.

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