New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: e mediated either by MITF, or requires a fully functional homeodomain or a specific subset of isoforms for activation of other target genes required for these processes. Conclusion Recently it has been proposed that melanoma, and tumours in general, contain tumour “stem” cells harbouring metastatic potential [145,146,239‐242]. Given that melanoma stem cells may promote tumour growth and metastasis 50 Chapter II – Medic and Ziman, 2009 [143,144,147,243] and since PAX3 is involved in maintenance of progenitor cells [19,122,244], its role in melanoma may be similar, i.e. to maintain the melanoma stem cell population. Further experiments to confirm this are underway. Based upon the molecular signature of melanocyte stem cells in the bulge are of the hair follicle ‐ i.e. positive for Pax3 and Wnt inhibitors, but negative for Mitf and its downstream melanogenic targets [150] ‐ it seems likely that the melanoma stem cells would have a similar signature. Indeed, melanoma stem cells are in fact quiescent, slow growing, non‐melanised cells with a stem cell marker signature, including ABCB5 [144,240]. Based on the information provided in this review, it is clear that the expression of PAX3 in melanoma is much more than merely a marker of the cell lineage. It may in fact be a key factor in determining melanoma cell fate as well as its migratory properties, thus influencing its metastatic potential and ultimately the course of the disease. Further research to clarify its specific role(s) in melanoma is required. Acknowledgement Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. 51 Chapter III – Medic and Ziman, 2010 Chapter III EXPERIMENTAL ARTICLE PAX3 Expression in Normal Skin Melanocytes and Melanocytic Lesions (Naevi and Melanomas) Authors and Affiliations Sandra Medic1 and Mel Ziman1,2* 1 School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia 2 School of Pathology and Laboratory Medicine, University of Western A...
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