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Article: Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers

TitleExpression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2007
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2007, v. 67 n. 10, p. 4638-4647 How to Cite?
AbstractNicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR α6 (P < 0.001) and β3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR α4 (P < 0.001) and β4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR α6β3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR α1, α5, and α7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR α633 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer. ©2007 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/91593
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLam, DCLen_HK
dc.contributor.authorGirard, Len_HK
dc.contributor.authorRamirez, Ren_HK
dc.contributor.authorChau, WSen_HK
dc.contributor.authorSuen, WSen_HK
dc.contributor.authorSheridan, Sen_HK
dc.contributor.authorTin, VPCen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorWong, MPen_HK
dc.contributor.authorShay, JWen_HK
dc.contributor.authorGazdar, AFen_HK
dc.contributor.authorLam, WKen_HK
dc.contributor.authorMinna, JDen_HK
dc.date.accessioned2010-09-17T10:21:53Z-
dc.date.available2010-09-17T10:21:53Z-
dc.date.issued2007en_HK
dc.identifier.citationCancer Research, 2007, v. 67 n. 10, p. 4638-4647en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91593-
dc.description.abstractNicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChR) on bronchial epithelial cells, can regulate cellular proliferation and apoptosis via activating the Akt pathway. Delineation of nAChR subtypes in non-small-cell lung cancers (NSCLC) may provide information for prevention or therapeutic targeting. Expression of nAChR subunit genes in 66 resected primary NSCLCs, 7 histologically non-involved lung tissues, 13 NSCLC cell lines, and 6 human bronchial epithelial cell lines (HBEC) was analyzed with quantitative PCR and microarray analysis. Five nonmalignant HBECs were exposed to nicotine in vitro to study the variation of nAChR subunit gene expression with nicotine exposure and removal. NSCLCs from nonsmokers showed higher expression of nAChR α6 (P < 0.001) and β3 (P = 0.007) subunit genes than those from smokers, adjusted for gender. In addition, nAChR α4 (P < 0.001) and β4 (P = 0.029) subunit gene expression showed significant difference between NSCLCs and normal lung. Using Affymetrix GeneChip U133 Sets, 65 differentially expressed genes associated with NSCLC nonsmoking nAChR α6β3 phenotype were identified, which gave high sensitivity and specificity of prediction. nAChR α1, α5, and α7 showed significant reversible changes in expression levels in HBECs upon nicotine exposure. We conclude that between NSCLCs from smokers and nonsmokers, different nAChR subunit gene expression patterns were found, and a 65-gene expression signature was associated with nonsmoking nAChR α633 expression. Finally, nicotine exposure in HBECs resulted in reversible differences in nAChR subunit gene expression. These results further implicate nicotine in bronchial carcinogenesis and suggest targeting nAChRs for prevention and therapy in lung cancer. ©2007 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshBronchi - cytologyen_HK
dc.subject.meshCarcinoma, Non-Small-Cell Lung - genetics - metabolismen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshEpithelial Cells - drug effects - metabolism - physiologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLung Neoplasms - genetics - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshNicotine - pharmacologyen_HK
dc.subject.meshOligonucleotide Array Sequence Analysisen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshRNA, Messenger - biosynthesis - geneticsen_HK
dc.subject.meshReceptors, Nicotinic - biosynthesis - geneticsen_HK
dc.subject.meshSmoking - adverse effects - genetics - metabolismen_HK
dc.titleExpression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokersen_HK
dc.typeArticleen_HK
dc.identifier.emailLam, DCL:lamcl@hkucc.hku.hken_HK
dc.identifier.emailChung, LP:lpchung@hkucc.hku.hken_HK
dc.identifier.emailWong, MP:mwpik@hkucc.hku.hken_HK
dc.identifier.authorityLam, DCL=rp01345en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityWong, MP=rp00348en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-06-4628en_HK
dc.identifier.pmid17510389-
dc.identifier.scopuseid_2-s2.0-34250307900en_HK
dc.identifier.hkuros134765-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34250307900&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume67en_HK
dc.identifier.issue10en_HK
dc.identifier.spage4638en_HK
dc.identifier.epage4647en_HK
dc.identifier.isiWOS:000246778500011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLam, DCL=7201749615en_HK
dc.identifier.scopusauthoridGirard, L=7101715512en_HK
dc.identifier.scopusauthoridRamirez, R=36869107800en_HK
dc.identifier.scopusauthoridChau, WS=13305781500en_HK
dc.identifier.scopusauthoridSuen, WS=12786607600en_HK
dc.identifier.scopusauthoridSheridan, S=7006840029en_HK
dc.identifier.scopusauthoridTin, VPC=6603199735en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridWong, MP=7403907887en_HK
dc.identifier.scopusauthoridShay, JW=7103373158en_HK
dc.identifier.scopusauthoridGazdar, AF=35372587300en_HK
dc.identifier.scopusauthoridLam, WK=7203021937en_HK
dc.identifier.scopusauthoridMinna, JD=35380041500en_HK
dc.identifier.citeulike2642175-

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