title: Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production.
abstract: Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclear DNA-binding activity of NF-κB and transcriptional activity through constitutive IκBα phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-κB activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.
authors.affiliation: Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Jin Sil
authors.initials: JS
authors.lastname: Chung
authors.affiliation: Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Lee
authors.affiliation: Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea. Electronic address: ydy1130@korea.ac.kr.
authors.forename: Young Do
authors.initials: YD
authors.lastname: Yoo
mesh_terms: D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; C513338:ROMO1 protein, human; D017382:Reactive Oxygen Species
keywords: Hepatocellular carcinoma; Nuclear factor-kappa B; Oxidative stress; Reactive oxygen species; Romo1; Tumor growth