Differential Expression of Aquaporins and Its Diagnostic Utility in Thyroid Cancer 英文参考文献.docVIP

DifferentialExpressionofAquaporinsandItsDiagnostic UtilityinThyroidCancer DongfengNiu1,TetsuoKondo1,TadaoNakazawa1,TomonoriKawasaki1,TetsuYamane1, KunioMochizuki1,YohichiroKato3,ToshiyukiMatsuzaki2,KuniakiTakata2,RyoheiKatoh1* 1DepartmentofHumanPathology,UniversityofYamanashiInterdisciplinaryGraduateSchoolofMedicineandEngineering,Yamanashi,Japan,2DepartmentofAnatomy andCellBiology,GunmaUniversityGraduateSchoolofMedicine,Maebashi,Japan,3DepartmentofPathology,TokyoWomen’sMedicalUniversityGraduateSchoolof Medicine,Tokyo,Japan Abstract Background: Aquaporin3 (AQP3) and Aquaporin4 (AQP4) play a major role in transcellular and transepithelial water movement as water channel membrane proteins. Little is known of their expression and significance in human thyroid tissues. Thus, we examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunctionwithhumanthyroidcancercelllines. MethodsandResults:ImmunohistochemicalanalysesdemonstratedAQP3inthecytoplasmicmembraneofnormalCcells, butnotinfollicularcells.Incontrast,AQP4wasnotfoundinCcellsbutwasidentifiedinnormalfollicularcells.AQP4was positivein92%ofGraves’diseasethyroidsand97%ofmultinodulargoiters,andwefailedtodemonstrateAQP3inthese hyperplastic tissues. In neoplastic thyroid lesions, we observed AQP3 in 91% of medullary thyroid carcinomas but in no otherfollicularcelltumors.AQP4wasdemonstratedin100%offollicularadenomas,90%offollicularcarcinomas,and85% of papillary carcinomas, while it was negative in all medullary carcinomas and undifferentiated carcinomas. Reverse transcriptasepolymerasechainreaction(RT-PCR)analysesrevealedAQP3mRNAexpressiononlyinmedullarycarcinomas andAQP4mRNAexpressioninfollicularcell-derivedtumorsexceptforundifferentiatedcarcinomas.Inthyroidcancercell lines,usingRT-PCRandwesternblotting,AQP3mRNAandproteinwereonlyidentifiedintheTTcellline(humanmedullary carcinoma cell line) and AQP4 in the other cell lines. In addition, AQP3 mRNA expression was up-regulated by