NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor
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...
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doaj-43389d3ee02140089f98a403403bd9e92020-11-24T21:47:41ZengMDPI AGInternational Journal of Environmental Research and Public Health1660-46012014-12-01121648210.3390/ijerph120100064ijerph120100064NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor SuppressorGuang Cheng0Jianmin Li1Maoguen Zheng2Yinzhi Zhao3Jing Zhou4Wande Li5The Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, ChinaThe Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, ChinaThe Central Lab, Hebei United University Affinity Hospital, Tangshan 063000, ChinaDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USADepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USADepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USAA 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.http://www.mdpi.com/1660-4601/12/1/64lysyl oxidase (LOX)4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)CpG methylationhistone H3 acetylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guang Cheng Jianmin Li Maoguen Zheng Yinzhi Zhao Jing Zhou Wande Li |
spellingShingle |
Guang Cheng Jianmin Li Maoguen Zheng Yinzhi Zhao Jing Zhou Wande Li NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor International Journal of Environmental Research and Public Health lysyl oxidase (LOX) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) CpG methylation histone H3 acetylation |
author_facet |
Guang Cheng Jianmin Li Maoguen Zheng Yinzhi Zhao Jing Zhou Wande Li |
author_sort |
Guang Cheng |
title |
NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor |
title_short |
NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor |
title_full |
NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor |
title_fullStr |
NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor |
title_full_unstemmed |
NNK, a Tobacco-Specific Carcinogen, Inhibits the Expression of Lysyl Oxidase, a Tumor Suppressor |
title_sort |
nnk, a tobacco-specific carcinogen, inhibits the expression of lysyl oxidase, a tumor suppressor |
publisher |
MDPI AG |
series |
International Journal of Environmental Research and Public Health |
issn |
1660-4601 |
publishDate |
2014-12-01 |
description |
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. |
topic |
lysyl oxidase (LOX) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) CpG methylation histone H3 acetylation |
url |
http://www.mdpi.com/1660-4601/12/1/64 |
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