M.Xuetal./Pathology–ResearchandPractice210(2014)397–401
401
paraf n-embeddedslices,whichshowedthatCullin1wascorrela-tivelyexpressedwithKi-67.BothCullin1andKi-67werehighlyexpressedinpoorlydifferentiatedNSCLCslices(Fig.2).Besides,Cullin1wassigni cantlyassociatedwithhistologicaldifferenti-ation(P=0.002),clinicalstage(P=0.010),andKi-67(P=0.021;Table1).MultivariateanalysisusingtheCox’sproportionalhazardsmodelindicatedthatCullin1mightbeanindependentindicatorofNSCLCpatients’prognosis(P=0.033;Table2).SurvivalcurverevealedthathighCullin1expressioncorrelatedwithpoorsurvivalwithstatisticalsigni cance(P<0.001;Fig.3).Thus,our ndingssupportedthenotionthatCullin1couldbeapositiveregulatorandpotentiallyatherapeutictargetofNSCLC.Sofar,thereisbarelyanystudyaboutCullin1inNSCLC;inthisstudywearethe rsttostudythefunctionofCullin1onNSCLC.
Insummary,wefoundthathighCullin1expressionwassigni -cantlyassociatedwithhighhistologicalgradeandKi-67expressionaswellaspoorprognosisinpatientswithNSCLC.However,alargergroupofpatientsneedstobeinvestigatedtocon rmthisconclu-sion.Consequently,Cullin1expressioncouldaffectoverallsurvivalwithtumorprogressionandthusrepresentedapotentialtargetforthetreatmentofNSCLC.Becausecellproliferationhadessen-tialrolesincarcinogenesis,controllingofcancercellproliferationwasimportantforinhibitingcancerprogression.Ourpresentstud-iessupportedanimportantroleforCullin1inpromotingNSCLCprogression,andsuggestedapossiblepathologicalmechanismofNSCLC.AlltheseindicatedthatCullin1mightfunctionasatherapytargetforNSCLC.Thereby,inordertoclarifythemolecularmecha-nismsofCullin1inNSCLCpathogenesis,furtherstudiesareofgreatnecessity.
Paraf n-embeddedtissuesectionswerestainedwithantibodiesforCullin1andKi-67andcounterstainedwithhematoxylin(A–L).BothCullin1andKi-67werehighlyexpressedinlungsquamouscellcarcinomacells(A,B,E,F,I,J)andlungadenocarcinomacells(C,D,G,H,K,L).AccordingtotheintensityofCullin1expression,wedividedthesamplesintohistologicdifferentiationgradeI(A–D),histologicdifferentiationgradeII(E–H),andhistologicdifferentiationgradeIII(I–L).
Kaplan–MeiersurvivalcurvesforlowversushighCullin1expressionon114patientswithNSCLCshowedahighlysigni cantseparationbetweencurves(P<0.001).
Con ictofinterest
Alltheauthorsdeclarenocon ictofinterest.
References
[1]J.Okamoto,T.Hirata,Z.Chen,H.M.Zhou,I.Mikami,etal.,EMX2isepigenetically
silencedandsuppressesgrowthinhumanlungcancer,Oncogene29(2010)5969–5975.
[2]A.Jemal,R.Siegel,J.Xu,E.Ward,Cancerstatistics,CA:CancerJ.Clin.60(2010)
277–300.
[3]B.B.Chen,J.R.Glasser,T.A.Coon,R.K.Mallampalli,F-boxproteinFBXL2exerts
humanlungtumorsuppressor-likeactivitybyubiquitin-mediateddegradationofcyclinD3resultingincellcyclearrest,Oncogene31(2012)2566–2579.
[4]S.Paul,Dysfunctionoftheubiquitin–proteasomesysteminmultipledisease
conditions:therapeuticapproaches,Bioessays30(2008)1172–1184.
[5]M.S.Hung,J.H.Mao,Z.Xu,C.T.Yang,J.S.Yu,etal.,Cul4Aisanoncogenein
malignantpleuralmesothelioma,J.Cell.Mol.Med.15(2011)350–358.
[6]H.Morikawa,M.Kim,H.Mimuro,C.Punginelli,T.Koyama,etal.,Thebacterial
effectorCifinterfereswithSCFubiquitinligasefunctionbyinhibitingdened-dylationofCullin1,mun.401(2010)268–274.
[7]K.I.Nakayama,K.Nakayama,Ubiquitinligases:cell-cyclecontrolandcancer,
Nat.Rev.Cancer6(2006)369–381.
[8]A.Mocciaro,M.Rape,Emergingregulatorymechanismsinubiquitin-dependentcellcyclecontrol,J.CellSci.125(2012)255–263.
[9]Q.Wang,W.Li,Y.Zhang,X.Yuan,K.Xu,etal.,Androgenreceptorregulatesa
distincttranscriptionprograminandrogen-independentprostatecancer,Cell138(2009)245–256.
[10]T.Murata,K.Takayama,S.Katayama,T.Urano,K.Horie-Inoue,etal.,miR-148ais
anandrogen-responsivemicroRNAthatpromotesLNCaPprostatecellgrowthbyrepressingitstargetCAND1expression,ProstateCancerProstaticDis.13(2010)356–361.
[11]M.Watanabe,T.Suzuki,M.Kim,Y.Abe,Y.Yoshida,etal.,Coronin7formsa
novelE3ubiquitinligasecomplextopromotethedegradationoftheanti-proliferativeproteinTob,FEBSLett.585(2011)65–70.
[12]J.Moon,G.Parry,M.Estelle,Theubiquitin–proteasomepathwayandplant
development,PlantCell16(2004)3181–3195.
[13]C.Ren,J.Pan,W.Peng,P.Genschik,L.Hobbie,etal.,PointmutationsinArabidop-sisCullin1revealitsessentialroleinjasmonateresponse,PlantJ.42(2005)514–524.
[14]R.J.Deshaies,SCFandCullin/RingH2-basedubiquitinligases,Annu.Rev.Cell
Dev.Biol.15(1999)435–467.
[15]A.Hershko,A.Ciechanover,Theubiquitinsystem,Annu.Rev.Biochem.67
(1998)425–479.
[16]Y.Xu,T.Sengupta,L.Kukreja,A.C.Minella,MicroRNA-223regulatescyclinE
activitybymodulatingexpressionofF-boxandWD-40domainprotein7,J.Biol.Chem.285(2010)34439–34446.
[17]G.Chen,G.Li,IncreasedCul1expressionpromotesmelanomacellproliferation
throughregulatingp27expression,Int.J.Oncol.37(2010)1339–1344.
[18]E.Reinstein,A.Ciechanover,Narrativereview:proteindegradationand
humandiseases:theubiquitinconnection,Ann.Intern.Med.145(2006)676–684.
[19]R.C.O’Hagan,M.Ohh,G.David,I.M.deAlboran,F.W.Alt,etal.,Myc-enhanced
搜索“diyifanwen.net”或“第一范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读,第一范文网,提供最新教学研究High expression of Cullin1 indicates poor prognosis for NSCLC patients(8)全文阅读和word下载服务。
相关推荐: