ssx is critical for cyclin d1 expression synovialsyt对滑膜中细胞周期蛋白表达至关重要.pdfVIP

[CANCERRESEARCH62,3861–3867,July1,2002]

SYT-SSXIsCriticalforCyclinD1ExpressioninSynovialSarcomaCells:AGainof

Functionofthet(X;18)(p11.2;q11.2)Translocation1

YuntaoXie,Bjo¨rnSkytting,GunnarNilsson,AlessandraGasbarri,KarlHaslam,ArmandoBartolazzi,

BerthaBrodin,NilsMandahl,andOlleLarsson2

DepartmentsofOncologyandPathology[Y.X.,K.H.,A.B.,B.B.,O.L.]andOrthopedics[G.N.],KarolinskaHospital,SE-17176Stockholm,Sweden;Departmentof

Orthopedics,StockholmSoderHospital,SE-11883Stockholm,Sweden[B.S.];DepartmentofClinicalGenetics,UniversityHospital,SE-22185Lund,Sweden[N.M.];

DepartmentofImmunology,ReginaElenaCancerInstitute,00158Rome,Italy[A.G.];DepartmentofOncology,ZhongnanHospital,WuhanUniversity,430071Wuhan,People’s

Republicof[Y.X.];andDepartmentofBiologicalScience,DublinInstituteofTechnology,Dublin2,Ireland[K.H.]

coma(12,13),indicatingthatthefusiongenemayleadtouncon-

trolledcellgrowth.Becauseuncontrolledcellgrowthisacrucialevent

TheSYT-SSXfusiongenehasbeenimplicatedinthemalignanttumorintumortransformationandprogression(14),afunctionalinteraction

cellgrowthofsynovialsarcoma,buttheunderlyingmolecularmecha-

betweenSYT-SSXandthecellcyclemachinerywouldconstitutean

nismsarestillpoorlyunderstood.HerewedemonstratethatSYT-SSXis

importantmechanismindevelopmentofsynovialsarcoma.

criticalfortheproteinlevelofcyclinD1insynovialsarcomacells.Anti-3

senseoligonucleotidestoSYT-SSXmRNArapidlyanddrasticallyde-ASODNshaveemergedasanimportanttoolingenefunctionand

creasedcyclinD1andsubsequentlyinhibitedcellgrowth.Thiseffectistargetvalidationbothinvitroandvivo(15).ASODNsbindto