Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis 英文参考文献.docVIP

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Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis 英文参考文献.doc

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Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis 英文参考文献

Rrp1b,aNewCandidateSusceptibilityGene forBreastCancerProgressionandMetastasis Nigel P.S.Crawford1,Xiaolan Qian2,Argyrios Ziogas4,Alex G.Papageorge2,Brenda J.Boersma3,Renard C.Walker1, Luanne Lukes1,William L.Rowe1,Jinghui Zhang1,Stefan Ambs3,Douglas R.Lowy2,Hoda Anton-Culver4, Kent W. Hunter1* 1LaboratoryofPopulationGenetics,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,2LaboratoryofCellularOncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 3 Laboratory of Human Carcinogenesis, National Cancer Institute, NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,4EpidemiologyDivision,DepartmentofMedicine,UniversityofCaliforniaIrvine,Irvine,California, UnitedStatesofAmerica A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independentapproaches.First,yeasttwo-hybrid,immunoprecipitation,andfunctionalassaysdemonstratedaphysical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouseandhumanmetastasisgeneexpressiondataitwasobservedthatextracellularmatrix(ECM)genesarecommon components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expressionquantitativetraitlocusanalysisofpolyomamiddle-Ttransgene-inducedmammarytumorwasperformed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantlyalteredECMgeneexpression,tumorgrowth,anddisseminationinmetastasisassays.Furthermore,agene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expressiondataset.Finally,constitutionalpolymorphismwithinRRP1Bwasfoundtobesignificantlyassociatedwith tumor progr