PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas) 英文参考文献.docVIP

PAX3ExpressioninNormalSkinMelanocytesand MelanocyticLesions(NaeviandMelanomas) SandraMedic1,MelZiman1,2* 1School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia, 2School of Pathology and Laboratory Medicine, UniversityofWesternAustralia,Perth,WesternAustralia,Australia Abstract Background:CutaneousMalignantMelanomaisanaggressiveformofskincancer,arisingincutaneousmelanocytes.The transcriptionfactorPAX3regulatesmelanocytespecificationfromneuralcrestcellsduringdevelopmentbutexpressionin differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanomastaging anddetection.Inthis study weanalysed theexpressionof PAX3across thespectrum of melanocytic cells,fromnormalmelanocytestocellsofbenignandmalignantlesionstobetterassessitsfunctioninthesevarioustissues. Pax3andPAX3(italicized)refertothemouseandhumangene,respectively;whereasPax3andPAX3(non-italicized)referto thecorrespondingmouseandhumanprotein. Methodology and Principal Findings: PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co- expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1confirmsPAX3asacellsurvivalregulator.PAX3wasalsoco-expressedwithmelanomacellmigrationmarkerMCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicatingtheirlessdifferentiatedproliferativephenotype. Conclusions and Signifi