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Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers
Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines con...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620221/ https://www.ncbi.nlm.nih.gov/pubmed/28978081 http://dx.doi.org/10.18632/oncotarget.18948 |
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author | Bordas, Anna Cedillo, José Luis Arnalich, Francisco Esteban-Rodriguez, Isabel Guerra-Pastrián, Laura de Castro, Javier Martín-Sánchez, Carolina Atienza, Gema Fernández-Capitan, Carmen Rios, Juan José Montiel, Carmen |
author_facet | Bordas, Anna Cedillo, José Luis Arnalich, Francisco Esteban-Rodriguez, Isabel Guerra-Pastrián, Laura de Castro, Javier Martín-Sánchez, Carolina Atienza, Gema Fernández-Capitan, Carmen Rios, Juan José Montiel, Carmen |
author_sort | Bordas, Anna |
collection | PubMed |
description | Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, β4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and under-representation of cancer-inhibiting α4β2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type. |
format | Online Article Text |
id | pubmed-5620221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56202212017-10-03 Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers Bordas, Anna Cedillo, José Luis Arnalich, Francisco Esteban-Rodriguez, Isabel Guerra-Pastrián, Laura de Castro, Javier Martín-Sánchez, Carolina Atienza, Gema Fernández-Capitan, Carmen Rios, Juan José Montiel, Carmen Oncotarget Research Paper Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, β4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and under-representation of cancer-inhibiting α4β2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type. Impact Journals LLC 2017-07-04 /pmc/articles/PMC5620221/ /pubmed/28978081 http://dx.doi.org/10.18632/oncotarget.18948 Text en Copyright: © 2017 Bordas et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Bordas, Anna Cedillo, José Luis Arnalich, Francisco Esteban-Rodriguez, Isabel Guerra-Pastrián, Laura de Castro, Javier Martín-Sánchez, Carolina Atienza, Gema Fernández-Capitan, Carmen Rios, Juan José Montiel, Carmen Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title | Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title_full | Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title_fullStr | Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title_full_unstemmed | Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title_short | Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
title_sort | expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620221/ https://www.ncbi.nlm.nih.gov/pubmed/28978081 http://dx.doi.org/10.18632/oncotarget.18948 |
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