p53基因和乳腺癌的相关性研究进展

291Vol.29No.120112EXPERIMENTALANDLABORATORYMEDICINEFeb.2011··p53；；，7～10%，，[1]，。，，p53，p5350%。p53[2]，、、、、、、、、、、、、。，5.8%()47.8%()[3]。p53，p53。15～50%p53[4]，p53Meta，p5345%[5]。p53，。1p53p5317p13.1，16～20kb，1110，，400bpp1，1kbp2，，CAAT、TATAGC。p532.5kbmRNA，393，53KD，p53[6]。p53N-、、DNA、、C-DNA。p53，175，245，248，273337[7]。p53Bax、Bak、Noxa、PUMA、p21、Gadd45，14-3-3。2p53P53，p53，，p53。P53，DNA，，DNA，，“”[8]。p53p53，，，p53，p53p53，，，[9]。p53，，，，。p53，p53，[10]。3p53，，，。(1)p53。p53p21，p21cyclin-CDK2cyclin-CDK4，G1。p53。、，p53，300、、、。(2)p53Bcl-2，p53[11]：TIGAR(TP53)，-2，6-，p53；DRAM[12]。(3)，。Wnt-β-catenin，p53Cadherin，β-catenin，，。(4)，p53，，。Teodoroetal[13-14]p53(，330006)R730.23,R737.9,Q344+.13C1674-1129(2011)01-0057-03doi:10.3969/j.issn.1674-1129.2011.01.024.：(30960430/H1601)57··291Vol.29No.120112EXPERIMENTALANDLABORATORYMEDICINEFeb.2011p53(PHDs)，，，p53：(HIF)；，(VEGF)、(bFGF)；。(5)p53(MDR)。p53，。(6)[15]p53p53，p53，mdm2，mdm4，bcl2p21，p53。4p53。p53p53。[16]p53。p53，p53，DNA,。Mottolese[17]7244，p53，p53。p53，，，，p53～。，[18]p53，p53，，。5p53p53。p53，[19]。DookeranKA[20]p53(54.7%)p53(66.7%)。p53，p53，，p53，，，，，，，，p53，[21]。p53，p53，，p53p63p73[22，23]，p63p73，p53，。p53，p73“p53”、DNA、p53p21。p73，，[24]，p63，，，。6p53，，“”[25]。，，，，。、，，p53，。p53，[26]。，188，p53[27]。p53，p53。，40%p53，[28]p53p53，，。，，p53，，，。7p53，，、，，，p53、、、，，，，p53，p53，、、。，。[1]Lvkovic-KapiclT,Knezevic-UsajS,PanjkovicM,etal.Theinflu-enceofagingonpathologicandimmunobiologicparametersofinva-siveductalbreastcarcinoma.[J].VojnosanitPregl,2006,63(11):921-927.58··291Vol.29No.120112EXPERIMENTALANDLABORATORYMEDICINEFeb.2011(46)(P=0.0251)，b30(P=0.3826)，。6DLi，DLi1.63%，2.5%，。x，y，0～23.0mmol/L，。[1],.—EP6-A[J].,2009,27(3):303-334.[2]ClinicalandLaboratoryStandardsInstitute.EvaluationoftheLinear-ityofQuantitativeMeasurmentProcedures[S].EP6-A2,CLSI,2003.[3],,.[J].,2007,25(4):342-360.[4]ClinicalandLaboratoryStandardsInstitute.Methodcomparisonandbiasestimationusingpatientsamples[S].EP9-A2,CLSI,2002.[2]SoussiT,BeroudC.AssessingTP53statusinhumantumorstoeval-uateclinicaloutcome[J].NatRevCancer,2001,1(3):233-240.[3]PetitjeanA,MatheE,KatoS,etal.Impactofmutantp53functionalpropertiesonTP53mutationpatternsandtumorphenotype:LessonsfromrecentdevelopmentsintheIARCTP53database[J].HumMu-tant,2007,28(6):622629.[4]DoTN,RosalRV,DrewL,etal.Preferentialinductionofnecrosisinhumanbreastcancercellbyap53peptidederivedfromtheMDM2bindingsite[J].Oncogene,2003,22(10):1431-1444.[5],,,.p53Meta[J].,2005,15(6):514-517.[6].p53[J].,2008,19(3):158-160.[7]WojcikI,SzybkaM,GolanskaE,etal.AbnormalitiesoftheP53,MDM2,BCL2andBAXgenesinacuteleukemia’s[J].Neoplasm,2005,52(4):318-324.[8]VousdenKH,LaneDP.p53inhealthanddisease[J].NatRevMolCellBicol,2007,8:275-283.[9]BartekJ,IggoR,GaannonJ,etal.Geneticandimmunochemicalanalysisofmutantp53inhumanbreastcancercellline[J].Onco-gene,1990,5(6):893-899.[10]NorbergT,KlaarS,KarfG,etal.Increasedp53mutationfrequen-cyduringtumorprogression-resultsfromabreastcancercohort[J].CancerRes,2001,61(22):8317-8321.[11]BensaadK,TsurutaA,SelakMA,etal.Ap53-inducibleregulatorofglycolsisandapoptosis[J].Cell,2006,126(1):107-120.[12]CreightonD,WilkinsonS,OpreyJ,etal.DRAM,ap53-inducedmodulatorofautophagy,iscriticalforapoptosis[J].Cell,2006,126(1):121-134.[13]TeodoroJG,ParkerAE,ZhuX,etal.p53-mediatedinhibitionofangiogenesisthroughupregulationofacollagenprolyhydroxylase[J].Science,2006,3(13):968-971.[14]TeodoroJG,EvansSK,GreenMR.Inhibitionoftumorangiogenesisbyp53;anewrolefortheguardianofthegenome[J].JMolMed,2007,85(11):1175-1186.[15]Abdel-FatahTM,PoweDG,AgboolaJ,etal.Thebiological,clini-calandprognosticimplicationsofp53transcriptionalpathwaysinbreastcancers[J].JPathol,2010,220(4):401-403.[16]RohanTE,LiSQ,HartwickR,etal.p53alterationsandproteinaccmulationinbenignbreasttissueandbreastcancerrisk:acohortstudy[J].CancerEpidemiolBiomarkersPrev,2006,15(7):1316-1323.[17]MottoleseM,DadasiEA,BottiC,etal.Phenotypicchangesofp53Her2,andFassysteminmultiplenormaltissuessurroundingbreastcancer[J].CellPhysiol,2005,204(1):106-112.[18].p53[J].,2009,11(8):115-116.[19]，，p53[J].,2000，15(5)：307-308.[20]DookeranKA,DignamJJ,FerrerK,etal.p53asaMarkerofProg-nosisinAfrican-AmericanWomenwithBreastCancer[J].AnnSurgOncol,2010,17(5):1398-1405.[21]MoriN,DelsiteR,NatarajanK,etal.Lossofp53functionincoloncancercellsresultsphosphochineandtotalcholine[J].Molecu-larImaging,2004,3(4):319-323.[22]HanS,SembaS,AbeT,etal.Infrequentsomaticmutationsofthep73geneinvarioushumancancers[J].EurJSurgOncology,1999,25(2):194-198.[23]MollUM,SladeN.p63andp73:Rolesindevelopmentandtumorformation[J].MolCancerRes,2004,2(7):371-386.[24]YangA,WalkerN,BronsonRetal.p73-deficientmicehaveneu-rological,phenomenalandinflammatorydefectsbutlacksponta-neoustumors[J].Nature,2000,404(6773):99-103.[25].HER-2、P53[J].,2008,48(32):1-3.[26]MatsuzawaSI,ReedJC.Siah-1,SIP,andEbicollaborateinanov-clpathwayforbeta-catenindegradationlinkedtop53responses[J].MolCell,2001,7(5):915-926.[27]KrogerN,Milde-LangoschK,RiethdorfS,etal.Prognosticandpredictiveeffectsofimmunohistochemicalfactorsinhighriskpri-marybreastcancerpatients[J].ClinCancerRes,2006,12(1):159-168.[28]ObermillerPS,T