New Perspectives on Melanoma_ The Role of PAX3

New Perspectives on Melanoma The Role of PAX3

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Unformatted text preview: ustralia, Perth, Western Australia * Corresponding author A/Prof. Mel Ziman School of Exercise, Biomedical and Health Sciences Edith Cowan University Joondalup Campus PH: +61‐8‐63045171 Fax: +61‐8‐63045717 Email: [email protected] Running Title: PAX3 in Melanocytes Citation: Medic S, Ziman M (2010) PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLoS One 5: e9977. Impact factor (2010): 4.411 ERA rank (2010): A 52 Chapter III – Medic and Ziman, 2010 Abstract Background: Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non‐italicized) refer to the corresponding mouse and human protein. 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 coexpressed with melanocyte markers, MITF and MLANA. Co‐expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co‐expressed with melanoma cell migration marker MCAM 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‐pos...
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This document was uploaded on 03/06/2014 for the course CHEMISTRY 12 at National University of Singapore.

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