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NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor

Author

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  • Guang Cheng

    (The Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, China)

  • Jianmin Li

    (The Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, China)

  • Maoguen Zheng

    (The Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, China)

  • Yinzhi Zhao

    (Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA)

  • Jing Zhou

    (Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA)

  • Wande Li

    (Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA)

Abstract

A tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is believed to contribute to the cancer burden in cigarette smokers. To evaluate NNK effects on the expression of lysyl oxidase (LOX), a tumor suppressor, we examined this enzyme at various levels in NNK-treated rat fetal lung fibroblasts (RFL6). Exposure of cells to NNK reduced levels of steady-states LOX mRNA and new transcript synthesis. NNK inhibited all LOX protein species in a dose-dependent manner. Although 300 µM NNK markedly decreased the level in the 46 kDa preproenzyme, under same conditions, there was no detectable amounts of the 50 kDa proenzyme and the 32 kDa mature enzyme suggesting NNK perturbing the LOX protein processing to its mature form. Moreover, NNK also suppressed LOX activities in conditioned media of treated cells. At the promoter level, NNK enhanced methylation of CpG, but decreased acetylation of histone H3 at the core promoter region of the LOX gene. These results indicated that transcriptional and translational processes of LOX are major targets for NNK. Thus, inactivation of tumor suppressor gene LOX may play a critical role in NNK carcinogenesis.

Suggested Citation

  • Guang Cheng & Jianmin Li & Maoguen Zheng & Yinzhi Zhao & Jing Zhou & Wande Li, 2014. "NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor," IJERPH, MDPI, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:gam:jijerp:v:12:y:2014:i:1:p:64-82:d:43842
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    References listed on IDEAS

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    1. Janine T. Erler & Kevin L. Bennewith & Monica Nicolau & Nadja Dornhöfer & Christina Kong & Quynh-Thu Le & Jen-Tsan Ashley Chi & Stefanie S. Jeffrey & Amato J. Giaccia, 2006. "Lysyl oxidase is essential for hypoxia-induced metastasis," Nature, Nature, vol. 440(7088), pages 1222-1226, April.
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    Cited by:

    1. Minghui Ji & Yudong Zhang & Na Li & Chao Wang & Rong Xia & Zhan Zhang & Shou-Lin Wang, 2017. "Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13," IJERPH, MDPI, vol. 14(10), pages 1-13, October.

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    More about this item

    Keywords

    lysyl oxidase (LOX); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); CpG methylation; histone H3 acetylation;
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    JEL classification:

    • H3 - Public Economics - - Fiscal Policies and Behavior of Economic Agents

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