The role of nitric oxide in cancer

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摘要 Nitricoxide(NO)isapleiotropicregulator,criticaltonumerousbiologicalprocesses,includingva-sodilatation,neurotransmissionandmacrophage-mediatedimmunity.Thefamilyofnitricoxidesynthases(NOS)comprisesinducibleNOS(iNOS),endothelialNOS(eNOS),andneuronalNOS(nNOS).Interest-ingly,variousstudieshaveshownthatallthreeisoformscanbeinvolvedinpromotingorinhibitingtheetiologyofcancer.NOSactivityhasbeendetectedintumourcellsofvarioushistogeneticoriginsandhasbeenassociatedwithtumourgrade,proliferationrateandexpressionofimportantsignalingcomponentsassociatedwithcancerdevelopmentsuchastheoestrogenreceptor.ItappearsthathighlevelsofNOSexpression(forexample,generatedbyactivatedmacrophages)maybecytostaticorcytotoxicfortumorcells,whereaslowlevelactivitycanhavetheoppositeeffectandpromotetumourgrowth.Paradoxicallytherefore,NO(andrelatedreactivenitrogenspecies)mayhavebothgenotoxicandangiogenicproperties.IncreasedNO-generationinacellmayselectmutantp53cellsandcontributetotumourangiogenesisbyupregulatingVEGF.Inaddition,NOmaymodulatetumourDNArepairmechanismsbyupregulatingp53,poly(ADP-ribose)polymerase(PARP)andtheDNA-dependentproteinkinase(DNA-PK).Anunderstand-ingatthemolecularleveloftheroleofNOincancerwillhaveprofoundtherapeuticimplicationsforthediagnosisandtreatmentofdisease.
机构地区 不详
出处 《细胞研究:英文版》 2002年5期
出版日期 2002年05月15日(中国期刊网平台首次上网日期,不代表论文的发表时间)
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