Loss of GATA3 in bladder cancer promotes cell migration and invasion.pdf

KEYWORDS: Cancer Biol Ther. 2014 Apr;15(4):42835. doi: 10.4161/cbt.27631. Epub 2014 Jan 21. Loss of GATA3 in bladder cancer promotes cell migration and invasion. Li Y , Ishiguro H , Kawahara T , Kashiwagi E , Izumi K , Miyamoto H . Abstract The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in highgrade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a nonneoplastic urothelial line SVHUC. Knockdown of GATA3 in the bladder cancer lines (5637, TCCSUP, J82) resulted in promotion of cell migration and invasion as well as increases in the expression of their related molecules, such as vascular endothelial growth factor, matrix metalloproteinase (MMP)2, and MMP9, and the activity of MMP2 and MMP9. GATA3 loss was also associated with an increasing level of a mesenchymal marker Ncadherin and a decreasing level of an epithelial marker βcatenin. Consistent with these findings, enforced expression of GATA3 in UMUC3 inhibited cell migration and invasion. However, GATA3 showed marginal effects on bladder cancer cell viability and the expression of cell cycle or apoptosisrelated molecules. Additionally, in contrast to bladder cancer lines, no significant effects of GATA3 silencing on cell migration were seen in SVHUC. These findings suggest that GATA3 plays an important role in the prevention of bladder cancer progression and metastasis by inhibiting cell migration and invasion as well as epithelialtomesenchymal transition. GATA3; bladder cancer; cell invasion; cell migration; cell proliferation PMID: 24448324 [PubMed indexed for MEDLINE] PMCID: PMC3979820 Free PMC Article Abstract 1 2 2 3 4 2 Author information MeSH Terms, Substances LinkOut more resources Full text links PubMed

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Transcript of Loss of GATA3 in bladder cancer promotes cell migration and invasion.pdf

28/4/2015 LossofGATA3inbladdercancerpromotescellmigrationandinvasion.PubMedNCBI

http://www.ncbi.nlm.nih.gov/pubmed/24448324# 1/2

KEYWORDS:

CancerBiolTher.2014Apr15(4):42835.doi:10.4161/cbt.27631.Epub2014Jan21.

LossofGATA3inbladdercancerpromotescellmigrationandinvasion.LiY ,IshiguroH ,KawaharaT ,KashiwagiE ,IzumiK ,MiyamotoH .

AbstractThetranscriptionfactorGATA3isknownasabreasttumorsuppressoraswellasaurothelialmarker,anditslossisoftenseeninhighgradeinvasivebladdercancer.Nonetheless,GATA3functionsinbladdercancercellsremainlargelyunknown.Inthisstudy,weassessedtheeffectsofGATA3silencingviaRNAinterferenceoncellmigration,invasion,andproliferationofbladdercancer.GATA3expressionwasdownregulatedinallfourbladdercancerlinesexamined,comparedwithanonneoplasticurotheliallineSVHUC.KnockdownofGATA3inthebladdercancerlines(5637,TCCSUP,J82)resultedinpromotionofcellmigrationandinvasionaswellasincreasesintheexpressionoftheirrelatedmolecules,suchasvascularendothelialgrowthfactor,matrixmetalloproteinase(MMP)2,andMMP9,andtheactivityofMMP2andMMP9.GATA3losswasalsoassociatedwithanincreasinglevelofamesenchymalmarkerNcadherinandadecreasinglevelofanepithelialmarkercatenin.Consistentwiththesefindings,enforcedexpressionofGATA3inUMUC3inhibitedcellmigrationandinvasion.However,GATA3showedmarginaleffectsonbladdercancercellviabilityandtheexpressionofcellcycleorapoptosisrelatedmolecules.Additionally,incontrasttobladdercancerlines,nosignificanteffectsofGATA3silencingoncellmigrationwereseeninSVHUC.ThesefindingssuggestthatGATA3playsanimportantroleinthepreventionofbladdercancerprogressionandmetastasisbyinhibitingcellmigrationandinvasionaswellasepithelialtomesenchymaltransition.

GATA3bladdercancercellinvasioncellmigrationcellproliferation

PMID:24448324[PubMedindexedforMEDLINE] PMCID:PMC3979820 FreePMCArticle

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28/4/2015 LossofGATA3inbladdercancerpromotescellmigrationandinvasion.PubMedNCBI

http://www.ncbi.nlm.nih.gov/pubmed/24448324# 2/2

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