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FoliaMedicaLodziensia,2014,41/2:111-119
TheeffectofDNAmethyltransferaseandhistonedeacetylase
inhibitorsonαKlothogeneexpressioninbladdercancerT24cellline
WpływinhibiotorówmetylotransferazDNAorazdeacetylazbiałek
histonowychnaekspresjęgenuαKlothowkomórkachrakapęcherza
moczowegoliniiT24
AGNIESZKASZYMCZYK,EWAFORMA
KatedraCytobiochemii,WydziałBiologiiiOchronyŚrodowiska,
UniwersytetŁódzki
Abstract
Introduction:αKlothogenewasoriginallyidentifiedasaputativeage-
suppressinggeneinmice.RecentlyitisknownthatαKlothogenefunctionsas
atumorsuppressorinmanytypesofcancer,includingbreast,pancreas,gastric,
colon,lungandcervicalcancer.ThedownregulationofαKlothoexpressionwas
associatedwithCpGhipermethylationofpromoterregionandhistone
deacetylation.Bladdercanceristhemostcommoncanceroftheurinarytract
inPolishpopulation.TheaimofthisstudywastheanalysisoftheeffectofDNA
methyltransferaseandhistonedeacetylaseinhibitorsonαKlothogene
expressioninbladdercancercells.
Materialsandmethods:InthisstudyT24bladdercancercelllinewasused.
TheanalysisoftheeffectofDNAmethyltransferaseandhistonedeacetylase
inhibitorsonαKlothogeneexpressionwasperformedusingRealTimePCR
methodwithTaqManprobes.TodeterminethemethylationprofileofαKlotho
genepromoterregionquantitiveMethylation-SpecificPolymeraseChain
Reactiontechniquewasused.
Results:ThetreatmentofT24cellswithDNAmethyltransferaseinhibitor(AZA)
restoredtheexpressionofαKlothogene.AfterAZAtreatment,themethylation
levelofCpGislandinthepromoterregionofαKlothogenewasnearlyhalflower
(p<0.05)thancontrolcells.IncaseofthetreatmentofT24cellswithhistone
deacetylaseinhibitor(TSA)wedidnotobserveanychangesinαKLgene
expressioninrespecttothecontrolcells.Treatmentcellswithboththeinhibitors
ledtothesignificantincreaseofmRNAαKlothogeneexpressionlevel
(p<0.001).
Conclusions:ThechangesinαKlothogeneexpressiononmRNAlevelare
associatedwithepigeneticchanges.
Keywords:bladdercancer,klotho,DNAmethylation,histonedeacetylation
Adresdokorespondencji:DrEwaForma,KatedraCytobiochemii,UniwersytetŁódzki,
ul.Pomorska141/143,90-236Łódź,tel.+426354371,e-mail:eforma@biol.uni.lodz.pl
