Adiponectin Haploinsufficiency Promotes Mammary Tumor Development in MMTV-PyVT Mice by Modulation of Phosphatase and Tensin Homolog Activities 英文参考文献.docVIP

AdiponectinHaploinsufficiencyPromotesMammary TumorDevelopmentinMMTV-PyVTMicebyModulation ofPhosphataseandTensinHomologActivities JaniceB.B.Lam1,2,3,7.,KimH.M.Chow1,2,3.,AiminXu1,2,3,KarenS.L.Lam2,3,JingLiu1,2,3 ,Nai-Sum Wong4,RandallT.Moon6,PeterR.Shepherd8,GarthJ.S.Cooper8,YuWang1,3,5* 1Department ofPharmacology and Pharmacy, UniversityofHong Kong, HongKong, China,2Department ofMedicine, University ofHongKong, HongKong, China, 3ResearchCenterofHeart,Brain,Hormone,andHealthyAging,UniversityofHongKong,HongKong,China,4DepartmentofBiochemistry,UniversityofHongKong, HongKong,China,5OpenLaboratoryofChemicalBiologyoftheInstituteofMolecularTechnologyforDrugDiscoveryandSynthesis,UniversityofHongKong,Hong Kong, China, 6Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington, United States of America, 7School of Biological Sciences,UniversityofAuckland,Auckland,NewZealand,8MauriceWilkinsCentreforMolecularBiodiscovery,UniversityofAuckland,Auckland,NewZealand Abstract Background:Adiponectinisanadipokinepossessingbeneficialeffectsonobesity-relatedmedicalcomplications.Anegative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectindeficiencyinmammarycarcinogenesisremainselusive. Methodology/Principal Findings: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic micewithreducedadiponectinexpressionswereestablishedandthestromaleffectsofadiponectinhaploinsufficiencyon mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressivephenotype,wasderivedfromadiponectinhaplodeficientMMTV-PyVTmice.Comparingwiththosefromcontrol MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cult