oncogenetumor suppressor gene growth factorWord下载.docx
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oncogenetumor suppressor gene growth factorWord下载.docx
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oncogenetumorsuppressorgenegrowthfactor@#@Oncogenes,tumor-suppressorgenesandgrowthfactors@#@Cellproliferation,differentiationandapoptosisplayimportantrolesinlifeprocesses.Theyareaffectedandregulatedbymanyfactors,includingcancergenesandgrowthfactors.Iftheyarenotnormallyregulatedorcontrolled,cancersandotherdiseasesmayoccur.@#@Cancerisfundamentallyadiseaseofregulationfailureoftissuegrowthbyalterationsinoncogenes,tumor-suppressorgenesandmicroRNAgenes.Thealterationsareusuallysomaticevents,althoughgerm-linemutationscanpredisposeapersontoheritableorfamilialcancer.@#@Oncogenesaregenespotentialtocausecancerbypromotingcellgrowthandreproduction.Tumorsuppressorgenesaregenesexperimentallypotentialto“brake”cellmalignancydeepeningbyinhibitingcelldivisionandsurvival.Malignanttransformationcanoccurthroughtheformationofnoveloncogenes,theinappropriateover-expressionofnormaloncogenes,orbytheunder-expressionordisablingoftumorsuppressorgenes.Typically,sequentialalterationsinmanygenesarerequiredtotransformanormalcellintoacancercell.Soitisimportanttokeeptheideainyourmindthattheoccurrenceanddevelopmentofcancerisacomplicatedproceduresofmulti-stepsinvolvingmulti-genesandmulti-factors,suchaschemicals,physicalagents,viruses,hormones,growthfactorsandothers.@#@1Oncogenes@#@1.1Definitionofviraloncogene,cellularoncogeneandproto-oncogene@#@Oncogenesaregenesthathavethepotentialtocausecancer,theyareclassifiedintotwocategoriesbysource,oneisviraloncogenes(v-onc)whicharetheregionsintheviralgenome(DNAinDNAtumor-virusesorRNAinRNA-tumorviruses)thatcanbecarriedintoacellbythevirusandcausethehostcelltotakeonnewpropertiessuchasimmortalizationandanchorage-independentgrowth.Theotheristhecellularoncogenes(c-onc)existinginthecellgenomeandmostofthemhaveviralcounterparts.Whennotmutatedoractivated,cellularoncogenesarealsospeciallydesignatedasproto-oncogeneswhichareevolutionaryhighlyconservedgenesrequiredfornormalcellfunctionsincludingproliferationanddifferentiationandsotheyareindispensabletonormalhumandevelopmentandthemaintenanceoftissuesandorgans.Whenover-expressedintheabsolutenumberofproto-oncogeneproductsoractivatedatinappropriatetimesormutatedtoacquirethenewproperties,wesayproto-oncogenesareconvertedtooncogenesorcellularoncogeneswhichcaninducetransformation.Socellularoncogenesrefertoproto-oncogenesoractivatedproto-oncogenesorbothindifferentcases,whenrefertoactivatedproto-oncogenes,itisofthesamemeaningofoncogenesoractivatedoncogenes.@#@Therearetwowaystounderstandthatmostofcellularoncogenes(proto-oncogenes)havetheviralcounterparts.First,itmeansthesequencesofproto-oncogenesaresimilarbutnotidenticaltotheviralcounterparts:
@#@
(1)Thereareintronsinproto-oncogenesbutnotinviraloncogenes.
(2)Oftentherearemutationsorsequencelossesorinsertedsequencesintheviraloncogenescomparingwiththeproto-oncogenes,sotheviraloncogeneisfundamentallyactivatedorhighexpressedincellandoftransformingability.Second,somecellularoncogenesdonothavetheviralcounterpartsandviceversa.Todeepenunderstandingofthesentence,weshallbrieflytalkaboutvirusesandcancersnext.@#@1.2Virusesandcancer@#@Tumorcellsalsocanarisebynon-geneticmeansthroughtheactionsofspecifictumorviruses.@#@Therearetwoclassesoftumorviruses,DNAtumorvirusesandRNAtumorviruses,thelatteralsobeingreferredtoasretrovirusesforcontainingreversetranscriptase.RNAtumorvirusesarecommoninchickens,miceandcatsbutrareinhumans.TheonlycurrentlyknownhumanretrovirusesarethehumanT-cellleukemiaviruses(HTLVs)andtherelatedretrovirus,humanimmunodeficiencyvirus(HIV).@#@Accordingtothetransformingspeedofcells,RNAtumorvirusesareclassifiedintotwogroups,theyarechronicallytransformingviruseswhichdonotcontainviraloncogeneandacutelytransformingviruseswhichcontainviraloncogene,forexample,RSVcontainsanextragenev-srcwhichishomologoustoc-srcbutnotvitaltoitself.@#@InacutelytransformingvirusesofRNAtumorviruses,mostoftheviraloncogenesareoriginatedfromcellulargenesbyrecombinationbetweenaparentnon-transformingvirusandhostcellularDNA,whichmeansthecellularoncogeneshavebeentakenupintothegenomesofretrovirusesinthecauseofevolution.ButitistobenotedthatafewviraloncogenesofacutelytransformingRNAvirusesarenotoriginatedfromcellulargenesandneitheraretheviraloncogenesofDNAtumorviruses.@#@Therearetwowaysforavirustocausecancer:
@#@Itmaycarryoncogenesintoacelloritmayactivateacellularproto-
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