New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: ‐ repressor KAP1 on Pax3‐target promoters, namely MITF, TRP­1 and DCT, thus activating melanogenic program in a murine melanoma cell line B16F10 [339]. It is possible that similar mechanisms are involved in determining differential roles for PAX3 in melanocytes vs melanoma. However, the above mentioned modifications still have to be assessed in melanocytes and melanoma cells. Finally, PAX3 regulation of cell proliferation, migration and apoptosis in melanocytes and melanoma cells and the mechanism of PAX3 regulation of its downstream targets need to be confirmed in vitro. Several studies have reported effects of either exogenous PAX3 expression or PAX3 silencing on melanocyte and melanoma cell behaviour [27,28,163], but the effect of PAX3 silencing or 111 Chapter VI – Conclusion overexpression on the expression of PAX3 target genes identified in this study also need to be confirmed. Finally, these processes need to be confirmed in vivo. Overall, our findings support an importance of PAX3 for melanocytic lineage and give insight into its role in adult melanocytes. Moreover, they open a new perspective on melanoma progression and role of PAX3 in melanoma‐genesis. Here we have paved the way for future studies on the differential role of PAX3 in melanocytes and melanoma, and provided the basis for several prospective projects. 112 References 1. Medic S, Ziman M (2009) PAX3 across the spectrum: from melanoblast to melanoma. Crit Rev Biochem Mol Biol: 1‐13. 2. Medic S, Ziman M (2010) PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLoS One 5: e9977. 3. Medic S, Rizos H, Ziman M (2011) Differential PAX3 functions in normal skin melanocytes and melanoma cells. Biochem Biophys Res Commun 411: 832‐ 837. 4. Lewis TB, Robison JE, Bastien R, Milash B, Boucher K, et al. (2005) Molecular classification of melanoma using real‐time quantitative reverse transcriptase‐polymerase chain reaction. Cancer 104: 1678‐1686. 5. Diepgen TL, Mahler V (2002) The epidemiology of skin cancer. Br J Dermatol 146 Suppl 61: 1‐6. 6. Rigel DS (20...
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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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