Oncotarget

Research Papers:

Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers

Anna Bordas, José Luis Cedillo, Francisco Arnalich, Isabel Esteban-Rodriguez, Laura Guerra-Pastrián, Javier de Castro, Carolina Martín-Sánchez, Gema Atienza, Carmen Fernández-Capitan, Juan José Rios and Carmen Montiel _

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Oncotarget. 2017; 8:67878-67890. https://doi.org/10.18632/oncotarget.18948

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Abstract

Anna Bordas1,5,*, José Luis Cedillo1,5,*, Francisco Arnalich2,5,#, Isabel Esteban-Rodriguez3,5, Laura Guerra-Pastrián3,5, Javier de Castro4,5, Carolina Martín-Sánchez1,5, Gema Atienza1,5, Carmen Fernández-Capitan2,5, Juan José Rios2,5 and Carmen Montiel1,5,#

1Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain

2Servicios de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain

3Anatomía Patológica, Hospital Universitario La Paz, Madrid, Spain

4Oncología Médica, Hospital Universitario La Paz, Madrid, Spain

5Instituto de Investigaciones Sanitarias IdiPAZ, Madrid, Spain

*Co-first authors, These authors contributed equally to this work

#These authors have contributed equally to the direction of the work

Correspondence to:

Carmen Montiel, email: carmen.montiel@uam.es

Francisco Arnalich, email: farnalich@salud.madrid.org, francisco.arnalich@uam.es

Keywords: nAChRs, NSCLC, squamous cell carcinoma of the lung, lung adenocarcinoma, tobacco

Received: April 07, 2017     Accepted: June 17, 2017     Published: July 04, 2017

ABSTRACT

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.


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