Role of Sex Determining RegionYin EpithelialMesenchymal Transitionin Cervical Cancer
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Abstract
Background: Breastcancerisoneoftheleadingcauseofcancer-relateddeathsinwomenworldwideandincreasing
newlinerapidlyindevelopingcountries.Inthepresentstudy,weinvestigatedthepotentialroleandassociationofHSP70-2
newlinewithbreastcancer.
newlineMethods: HSP70-2expressionwasexaminedin154tumorand 103adjacentnon-canceroustissue(ANCT)
newlinespecimens andbreastcancercelllines(MCF7,BT-474,SK-BR-3 andMDA-MB-231)byRT-PCR,quantitative-PCR,
newlineimmunohistochemistry,Westernblotting,flowcytometryandindirectimmunofluorescence.Plasmiddriven
newlineshort hairpinRNAapproachwasemployedtovalidatetherole ofHSP70-2incellularproliferation,senescence,
newlinemigration,invasionandtumorgrowth.Further,westudiedtheeffectofHSP70-2proteinablationonsignaling
newlinecascadesinvolvedinapoptosis,cellcycleandEpithelial-Mesenchymal-Transitionbothincultureaswellasin-vivo
newlinehumanbreastxenograftmousemodel.
newlineResults: HSP70-2expressionwasdetectedinmajorityofbreastcancerpatients(83%)irrespective ofvarioushistotypes,
newlinestagesandgrades.HSP70-2expressionwasalsoobservedinallbreastcancercells(BT-474,MCF7,MDA-MB-231and
newlineSK-BR-3)usedinthisstudy.DepletionofHSP70-2inMDA-MB-231andMCF7cellsresultedinasignificantreductionin
newlinecellular growth,motility,onsetofapoptosis,senescence, cellcyclearrestaswellasreduction oftumorgrowthinthe
newlinexenograft model.Atmolecularlevel, down-regulation ofHSP70-2resultedin reducedexpressionofcyclins,cyclin
newlinedependentkinases,anti-apoptoticmoleculesandmesenchymalmarkersandenhancedexpressionofCDKinhibitors,
newlinecaspases,pro-apoptoticmoleculesandepithelialmarkers.
newlineConclusions: HSP70-2isoverexpressedinbreastcancerpatients and wasinvolvedinmalignantpropertiesofbreast
newlinecancer. ThissuggestsHSP70-2maybepotentialcandidatemolecule fordevelopmentofbetterbreastcancertreatment