Cell-differentiation-and-Cancer-cells.ppt

CelldifferentiationandCancercells,Celldifferentiation,Chapter12,1.Abouttheconceptofcelldifferentiation,Theprocessthatacellchangestocarryoutaspecializedfunction:Markedby:Morphology/Structure/Function,ThedifferentcelltypesofamulticellularorganismcontainthesameDNA.Acellcanchangetheexpressionofitsgenesinresponsetoexternalsignals.DifferencesinmRNAexpressionpatternsamongdifferentcelltypes.Differentcelltypessynthesizedifferentsetsofproteins.GeneexpressioncanberegulatedatmanyofthestepsinthepathwayfromDNAtoRNAtoprotein.,Thefouressentialprocessesbywhichamulticellularorganismismade:Cellproliferation,Cellspecialization,Cellinteraction,andCellmovement.,Celldifferentiationoccursinmulticellularorganisms,Human:1014cells,200celltypes,2.Whyafertilizedeggcandevelopintodifferentcells:Genedifferentiatedexpress,分子杂交技术检测基因及其表达,3.CombinationalcontrolandGenedifferentiatedexpresspp.416:12-1:2n(n=3,A,B,C),4.House-keepinggenesandluxurygenes,House-keepinggenes:Expressedinallcelltypes,essentialforallcells,Luxurygenes:Tissue-specificgenes,expressedinspecialcells,SequentialexpressionofvariousgenesinearlyDrosophilaembryo,5.Transdifferentiation:Fromonetypeofcellintoanothertype,Includes:Dedifferentiation-Redifferentiation,去分化,再分化,Celltotipotency(细胞全能性),1.Plantcells,Theabilityofacelldevelopsintoacompleteorganism,植物细胞具有全能性，在适宜条件下可培育成完整植株，已广泛应用,2.Animalcloning,Transplantationoffrogredcellnucleusindicatedthenucleusofanimalistotipotency(全能性),Aneworganismcreatedbytheprocessofnucleartransplantation,Dolly:Alambwithnofather,c,Thesheepstar:Dolly,克隆能给人类带来什么？,克隆动物是未来的制药厂,克隆的爱因斯坦会懂“相对论”吗,Stemcellanditsdifferentiationpotential,1.Whatisastemcell?,Hastwoabilities:(1)Self-renewing(2)Differentiating,2.Wheretogetthestemcells?,(1)Embryonicstemcells,(2)Adultstemcells,(3)Umbilicalcordbloodstemcells,(4)Fetalstemcells,3.Typesofstemcells:differentiationpotential,(1)Monopotentialstemcell,(2)Pluripotentstemcells,(3)Embryonicstemcells,Twowaysforastemcelltoproducedaughterswithdifferentfates,4.Whydoresearchersstudystemcells?,Forrepairingtissuedamagecausedbydiseaseorinjury,including:Diseasesthatimpairbrainfunction,suchasAlzheimersdiseaseandParkinsonsdiseaseSpinalcordinjuriesBlooddiseases,includingleukemiasBurns,5.Stemcellplasticity,Adultstemcellscandifferentiateintoalargenumberofdifferentcelltypes.,Turningbloodintobrain:Science,2000,290:1779-1782,Turningbrainintoblood:Science,1999,283:534-535,NSC+EGF不影响病毒复制，但影响细胞转化,1976年发现，正常鸡细胞核DNA中，具有与V-onc的同源序列，称正常细胞中的同源序列为原癌基因（protooncogene）,或C-oncogene.v-onc和c-onc的关系：c-onc来自v-onc.理由如下:1、v-onc对病毒复制和生存都是不必要的；而c-onc对细胞重要功能和活动不可缺少；提示c-onc是进化中保存下来的细胞重要结构元件。2、发现的30种c-onc是依靠病毒的v-onc探针找到的；并不是所有c-onc都有对应的同源v-onc。3、v-src缺失3/4不能致癌的RSV,注入鸡体内，发现缺失的v-src与c-src发生重组，v-src回复并致癌。,抑癌基因（tumorsuppressorgene）Harris(1968):癌细胞系与同组织正常细胞融合杂交细胞无恶性表型，也不致癌；随着染色体丢失则可能恢复致癌（Rb13q14.1）.,Proto-oncogenes,(1)Proto-oncogens:Gain-of-functionmutations,Rasoncogene:RetainbindGTP,Bcl-2oncogene:Preventapoptosis,(2)Tumorsuppressorgenes:Loss-of-functionmutations,Rbgene:Thefirsttumorsuppressorgeneinpatientwithretinoblastoma,p53:Guardianofthegenome,BecausetheaccumulationofgenemutationandNaturalselection,sothepatientisaged,Chartofthemajorsignalingpathwaysrelevanttocancerinhumancells,indicatingthecellularlocationsofsomeoftheproteinsmodifiedbymutationincancers.,Canwetreatcancer?,1.Conventionalapproachestocombatingcancer,SurgeryChemotherapy/Radiation,Cannotridofallcancercells,2.Genetherapy,Tumorcellslackfunctionaltumor-suppressorgenes,p53-bearingviruses,Engineeredadenovirus,Immuneresponse,3.Inhibitingtheformationofbloodvessels,Angiogenesis:Cancercellsgrowthfactorsendothelialcell