RGD Reference Report - ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. - Rat Genome Database

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ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus.

Authors: Improgo, Ma Reina D  Schlichting, Nicolette A  Cortes, Roxana Y  Zhao-Shea, Rubing  Tapper, Andrew R  Gardner, Paul D 
Citation: Improgo MR, etal., Mol Cancer Res. 2010 Feb;8(2):194-203. doi: 10.1158/1541-7786.MCR-09-0185. Epub 2010 Feb 2.
RGD ID: 150527851
Pubmed: PMID:20124469   (View Abstract at PubMed)
PMCID: PMC2824774   (View Article at PubMed Central)
DOI: DOI:10.1158/1541-7786.MCR-09-0185   (Journal Full-text)

Tobacco contains a variety of carcinogens as well as the addictive compound nicotine. Nicotine addiction begins with the binding of nicotine to its cognate receptor, the nicotinic acetylcholine receptor (nAChR). Genome-wide association studies have implicated the nAChR gene cluster, CHRNA5/A3/B4, in nicotine addiction and lung cancer susceptibility. To further delineate the role of this gene cluster in lung cancer, we examined the expression levels of these three genes as well as other members of the nAChR gene family in lung cancer cell lines and patient samples using quantitative reverse transcription-PCR. Overexpression of the clustered nAChR genes was observed in small-cell lung carcinoma (SCLC), an aggressive form of lung cancer highly associated with cigarette smoking. The overexpression of the genomically clustered genes in SCLC suggests their coordinate regulation. In silico analysis of the promoter regions of these genes revealed putative binding sites in all three promoters for achaete-scute complex homolog 1 (ASCL1), a transcription factor implicated in the pathogenesis of SCLC, raising the possibility that this factor may regulate the expression of the clustered nAChR genes. Consistent with this idea, knockdown of ASCL1 in SCLC, but not in non-SCLC, led to a significant decrease in expression of the alpha 3 and beta 4 genes without having an effect on any other highly expressed nAChR gene. Our data indicate a specific role for ASCL1 in regulating the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus. This regulation may contribute to the predicted role that ASCL1 plays in SCLC tumorigenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CHRNA5Humanlung adenocarcinoma  IEP mRNA:increased expression:lungRGD 
CHRNB4Humanlung adenocarcinoma  IEP mRNA:increased expression:lungRGD 
Chrna5Mouselung adenocarcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna5Ratlung adenocarcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Ratlung adenocarcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Mouselung adenocarcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 
CHRNA5Humanlung large cell carcinoma  IEP mRNA:increased expression:lungRGD 
Chrna5Mouselung large cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna5Ratlung large cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
CHRNA3Humanlung small cell carcinoma  IEP mRNA:increased expression:lungRGD 
CHRNA5Humanlung small cell carcinoma  IEP mRNA:increased expression:lungRGD 
CHRNB4Humanlung small cell carcinoma  IEP mRNA:increased expression:lungRGD 
Chrna3Ratlung small cell carcinoma  ISOCHRNA3 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna3Mouselung small cell carcinoma  ISOCHRNA3 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna5Mouselung small cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna5Ratlung small cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Ratlung small cell carcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Mouselung small cell carcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 
CHRNA5Humanlung squamous cell carcinoma  IEP mRNA:increased expression:lungRGD 
CHRNB4Humanlung squamous cell carcinoma  IEP mRNA:increased expression:lungRGD 
Chrna5Ratlung squamous cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrna5Mouselung squamous cell carcinoma  ISOCHRNA5 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Ratlung squamous cell carcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 
Chrnb4Mouselung squamous cell carcinoma  ISOCHRNB4 (Homo sapiens)mRNA:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Chrna3  (cholinergic receptor nicotinic alpha 3 subunit)
Chrna5  (cholinergic receptor nicotinic alpha 5 subunit)
Chrnb4  (cholinergic receptor nicotinic beta 4 subunit)

Genes (Mus musculus)
Chrna3  (cholinergic receptor, nicotinic, alpha polypeptide 3)
Chrna5  (cholinergic receptor, nicotinic, alpha polypeptide 5)
Chrnb4  (cholinergic receptor, nicotinic, beta polypeptide 4)

Genes (Homo sapiens)
CHRNA3  (cholinergic receptor nicotinic alpha 3 subunit)
CHRNA5  (cholinergic receptor nicotinic alpha 5 subunit)
CHRNB4  (cholinergic receptor nicotinic beta 4 subunit)


Additional Information