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Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model

BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide,...

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Autores principales: Kim, Seon-Kyu, Yun, Seok-Joong, Kim, Jiyeon, Lee, Ok-Jun, Bae, Suk-Chul, Kim, Wun-Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189956/
https://www.ncbi.nlm.nih.gov/pubmed/22028816
http://dx.doi.org/10.1371/journal.pone.0026131
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author Kim, Seon-Kyu
Yun, Seok-Joong
Kim, Jiyeon
Lee, Ok-Jun
Bae, Suk-Chul
Kim, Wun-Jae
author_facet Kim, Seon-Kyu
Yun, Seok-Joong
Kim, Jiyeon
Lee, Ok-Jun
Bae, Suk-Chul
Kim, Wun-Jae
author_sort Kim, Seon-Kyu
collection PubMed
description BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer.
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spelling pubmed-31899562011-10-25 Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model Kim, Seon-Kyu Yun, Seok-Joong Kim, Jiyeon Lee, Ok-Jun Bae, Suk-Chul Kim, Wun-Jae PLoS One Research Article BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer. Public Library of Science 2011-10-10 /pmc/articles/PMC3189956/ /pubmed/22028816 http://dx.doi.org/10.1371/journal.pone.0026131 Text en Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kim, Seon-Kyu
Yun, Seok-Joong
Kim, Jiyeon
Lee, Ok-Jun
Bae, Suk-Chul
Kim, Wun-Jae
Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title_full Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title_fullStr Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title_full_unstemmed Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title_short Identification of Gene Expression Signature Modulated by Nicotinamide in a Mouse Bladder Cancer Model
title_sort identification of gene expression signature modulated by nicotinamide in a mouse bladder cancer model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189956/
https://www.ncbi.nlm.nih.gov/pubmed/22028816
http://dx.doi.org/10.1371/journal.pone.0026131
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