New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: ding in the melanoma cells vs. melanocytes, also show a significant difference in expression levels. Melanoma specific PAX3 targets, NES and TPD52 show significant upregulation in A2058, whereas BCL2L1 is downregulated although this is not statistically significant. Also, PTEN is significantly downregulated in melanoma. Furthermore, targets that are common in melanoma and melanocytes, but show significantly higher PAX3 binding in melanoma (such as SOX9, MCAM and CSPG4) also show significant upregulation in A2058 suggesting a role for PAX3 in their increased activation. Discussion To elucidate the role of PAX3 in melanoma relative to its role in melanocytes, we focused on processes known to be regulated by PAX3 during melanocyte development that might also be critical for melanoma progression. Fourteen chosen genes associated with these processes were analysed here as potential PAX3 targets, and proved to be informative in clarifying PAX3 involvement not just in melanoma, but also in melanocyte cellular processes. Traditional developmental roles of PAX3 in regulating differentiation, proliferation, cell survival and migration, are retained in melanocytes and melanoma cells, utilising common pathways/ mediators (such are MITF, DCT, HES1, SOX9, CCNA2, TGFβ1, MCAM, CSPG4, and CXCR4). However, additional regulatory mechanisms are employed specifically in melanoma (exemplified by NES, TPD52, PTEN, and BCL2L1). Moreover, several of the common targets, namely SOX9, MCAM and CSPG4, show significant fold enrichment in melanoma cells compared to melanocytes, suggesting that PAX3 mediated mechanisms are amplified in melanoma. Interestingly, those targets that are more strongly activated in melanoma are those that determine a less differentiated (SOX9 and NES), more motile (MCAM and CSPG4) cell phenotype, characteristic of melanomas with a higher metastatic potential [125]. In addition PAX3 targets that appear 87 Chapter IV – Medic, Rizos and Ziman, 2011 restricted to melanom...
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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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