2 research outputs found
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 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 underrepresentation
of cancer-inhibiting α4β2-nAChR in ADC-L could explain the different
tobacco influences on the tumorigenic process in each cancer typeThis study was supported by grants to C. Montiel and F. Arnalich from the Ministry of Economy, Industry and Competitiveness, Government of Spain (SAF2014-56623-R) and Foundation “Mutua Madrileña Investigación Biomédica” (FMM2011), Spain. A.B.
is recipient of a fellowship (Beca FPI, Universidad AutĂłnoma Madrid). J.L.C. and C.M.S. are recipients of fellowships (Beca FPU from Ministerio de EducaciĂłn, Cultura y Deporte and Beca FPI from Ministry of Economy, Industry and Competitiveness, Government of Spain, respectively