New Perspectives on Melanoma_ The Role of PAX3

In this study we explore the multiple roles of pax3

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Unformatted text preview: is frequently found in melanomas and naevi, and its expression correlates with melanoma staging. In this study we explore the multiple roles of PAX3 in melanocyte genesis and melanoma progression. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during embryonic development, it is not clear if these same functions are maintained in adult melanocytes or melanoma cells. Drawing on evidence from development, we propose here a more encompassing theory that PAX3 is a key regulator of the myriad steps in melanocytic cell determination and function. We discuss the possibility that these roles may be accomplished by differential association with cofactors, via alternate transcripts or posttranslational protein modification(s). Moreover, we consider its possible roles in melanoma and provide a comprehensive consideration of the significance of PAX3 expression in melanoma. Methodology and Principal Findings: In this study we firstly analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions. PAX3 expression was analysed by immunohistochemistry and RT‐qPCR. In order to get a better understanding of PAX3 functions in these various tissues, we have characterised PAX3‐expressing cells with respect to their proliferative, migratory and antiapoptotic potential, as well as differentiation status. For this, immunofluorescence was used to analyse PAX3 co‐expression with markers representative of these processes that are also its downstream targets. iv Abstract As expected, PAX3 expression was observed in all naevi and melanoma samples, but it was also found in both follicular and epidermal melanocytes of normal skin. Melanocytic origin of PAX3‐expressing cells was confirmed by co‐expression with known melanocyte markers, MITF and MLANA. Co‐expression with its downstream target, antiapoptotic factor BCL2L1 confirmed PAX3 as a cell survival regulator. PAX3 was also co‐expressed with melanoma cell migration marker MCAM in dermal naevi, melanoma cell nests and normal melanocytes in growing hair follicles,...
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