BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells 英文参考文献.docVIP

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BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells 英文参考文献.doc

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BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells 英文参考文献

BLT2Up-RegulatesInterleukin-8Productionand PromotestheInvasivenessofBreastCancerCells HyunjuKim,Jung-AChoi,Geun-SooPark,Jae-HongKim* SchoolofLifeSciencesandBiotechnology,KoreaUniversity,Seoul,Korea Abstract Background:Theelevatedproductionofinterleukin(IL)–8iscriticallyassociatedwithinvasivenessandmetastaticpotential inbreastcancercells.However,theintracellularsignalingpathwayresponsibleforup-regulationofIL-8productioninbreast cancercellshasremainedunclear. Methodology/PrincipalFindings:Inthisstudy,wereportthattheexpressionofBLT2ismarkedlyup-regulatedinthehighly aggressivehumanbreastcancercelllinesMDA-MB-231andMDA-MB-435comparedwithMCF-10Aimmortalizedhuman mammary epithelial cells, asdetermined by RT-PCR,real-time PCR andFACSanalysis. Blockade of BLT2with BLT2 siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and thereby diminished the invasiveness of aggressive breast cancer cells, analyzed by Matrigel invasion chamber assays. We further characterized the downstream signalingmechanismbywhichBLT2stimulatesIL-8productionandidentifiedcriticalmediatoryrolesforthegenerationof reactiveoxygenspecies(ROS)andtheconsequentactivationofthetranscriptionfactorNF-kB.Moreover,blockadeofBLT2 suppressedtheformationofmetastaticlungnodulesbyMDA-MB-231cellsinbothexperimentalandorthotopicmetastasis models. Conclusions/Significance: Taken together, our study demonstrates that a BLT2–ROS–NF-kB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435 cells, thereby contributing to the invasiveness of these aggressive breast cancercells.Ourfindingsprovideinsightintothemolecularmechanismofinvasivenessinbreastcancer. Citation: Kim H, Choi J-A, Park G-S, Kim J-H (2012) BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells. PLoS ONE7(11):e49186.doi:10.1371/journal.pone.0049186 Editor:DennisJ.Templeton,UniversityofVirginia,UnitedStatesofAmerica ReceivedMay8,2012;AcceptedOctober3,2012;PublishedNovember7,2012 Copyright:?2