New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: [121] Χ [279] Χ [279] **(98th) [228] Χ [279] Table includes list of potential PAX3 target genes, their function, transcriptional regulation by PAX3 (up or downregulation), and presence of a PAX3 binding site; as well as literature references. Function is described as: differentiation (D), proliferation (P), migration (M), adhesion (Ad), apoptosis (Ap), angiogenesis (An), immune response (Im), and not defined (ND). Χ [4] indicates direct binding assessed by ChIP [281]; and χ [8] indicates presence of PAX3 binding site according to SABioscience database [282]. Single (*) or double asterisk (**), followed by the order number, indicate top downregulated or upregulated gene in melanoma vs. melanocytes, respectively [229]. 95 Chapter V – General Discussion Chapter V – General discussion Cutaneous melanoma is a neoplasm that arises from melanocytic cells in the skin. The transcription factor PAX3 is at the top of the hierarchy of factors that regulate melanocyte specification and differentiation, proliferation, survival and migration during embryonic development [10‐15]. PAX3 is also highly expressed in melanoma [2,21‐26], where it is shown to contribute to melanoma cell survival [27,28]. It is however not known whether PAX3 continues to control pathways of differentiation, proliferation and migration in melanoma cells and whether this contributes to melanoma progression. Taking into account the possibility that metastatic melanoma progression is driven by melanoma stem‐like cells, and taken together with the analogy between developmental processes and tumourigenesis, the pivotal role that PAX3 has during melanocyte development, has instigated us to further investigate PAX3 involvement in melanoma development and progression. PAX3 expression in melanocytic lesions and normal skin We initially started with a comparative analysis of PAX3 expression in normal skin, relative to its expression in a variety of melanocytic lesions, including benign pigmented naevi, and primary and metastatic melanomas, to see if c...
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