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1、埼玉医科大学雑誌 第31巻 第1号 平成16年1月33原 著Survivinの甲状腺濾胞上皮細胞増殖および分化に対する影響鈴木 美穂RoleofSurvivinontheProliferationandDifferentiationofThyroidEpithelialCellsMihoSuzuki（DepartmentofEndocrinologyandDiabetes,InstituteofInternalMedicine,SaitamaMedicalSchool,Moroyama,Iruma-
2、gun,Saitama350-0495,Japan）SurvivinisoneoftheIAP(inhibitorofapoptosisproteins),whichisexpressedduringembryonicdevelopment,butisnotexpressedinterminaldifferentiatedadulttissue.Overexpressionofsurvivinisobservedinavarietyofhumantumorsincludingthyroidcance
3、rs.Weexaminedtheroleofsurvivinontheproliferationanddifferentiationofthyroidepithelialcells.RatthyroidepithelialcelllineFRTL-5wasstablytransfectedwithhumansenseandantisensesurvivingenes.FRTL-5cellstransfectedwithasurvivinsensegene(Scells)proliferatedwit
4、houtTSH.InthepresenceofTSH,theproliferationofScellswassignificantlyfasterthanthatofcellstransfectedwithanemptyvector(Ecells)orcellstransfectedwithasurvivinantisensegene(AScells).TheproliferationofAScellswereretardedascomparedwiththatofEcells.Westernblo
5、tanalysisdemonstratedthatphosphorylationofRbproteinatserine795wasenhancedinScells.ActivationofE2F-1wasalsoenhancedinScellsasdemonstratedbygelshiftassay.NorthernblotanalysisshowedthatexpressionofPax-8mRNAwassignificantlyenhancedinScells,andwassignifican
6、tlydecreasedinAScells.Expressionofthyroglobulin(Tg)andTSHreceptor(TSHR)mRNAwasdecreasedinAScells.TherewasnosignificantchangeinTTF-1andTTF-2mRNAexpression.Theseobservationssuggestthatsurvivinenhancestheproliferationofthyroidepithelialcellsthroughactivat
7、ionofE2F-1,andalsoenhancetheexpressionofPax-8,whichthenaffecttheexpressionofthyroidspecificproteins.Survivinappearstoplayanimportantroleintheproliferationaswellasdifferentiationofthyroidepithelialcells.Keywords:Survivin,thyroidcancer,cellcycle,differen
8、tiation,Rbprotein,E2F-1,Pax-8,Tg,NIS,TSHRJSaitamaMedSchool2004;31:33-39(ReceivedNovember28,2003)transcriptionfactor-1（TTF-1）,thyroidtranscription緒言factor-2（TTF-2）などの転写因子は，thyroglobulin（Tg）,Survivin遺伝子は，胎生期の細胞や様々な癌細胞thyroidperoxidase（TPO
