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New Perspectives on Melanoma_ The Role of PAX3

Zimanecueduau

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Unformatted text preview: t PAX3 is the key regulator of similar cellular processes in both normal melanocytes and melanoma cell as observed in developing melanoblasts. We also hypothesise that by regulating the ‘plasticity’ of melanocytic cells, PAX3 enhances their tumourigenic potential and increases the aggressive phenotype of melanoma cells upon malignant transformation, thus contributing to melanoma progression. The primary aim of this project is to identify the role of the PAX3 in melanocytes and melanoma cells. Specific aims: 1. To compare the functions of PAX3 in melanoblasts, melanocytes and melanoma cells. 2. To assess PAX3 expression in normal skin and in a variety of melanocytic lesions (including benign naevi and malignant melanomas), and to characterise PAX3‐expressing cells with respect to markers of differentiation, proliferation, survival and migration. 3. To identify the roles of PAX3 by analysis of its target genes in melanocytes and in melanoma cells. Aim 1: To compare the functions of PAX3 in melanoblasts, melanocytes and melanoma cells. To address this aim, an intensive literature search was performed to identify the known roles for PAX3 during melanocyte development and melanoma‐genesis. The outcome of this study was an all encompassing view of the role of PAX3 in melanoma progression, published in Medic and Ziman, 2009, the first publication towards this thesis (Chapter II). 28 Chapter I – Thesis Overview Aim 2: To assess PAX3 expression in normal skin and in a variety of melanocytic lesions, and characterise PAX3­expressing cells with respect to markers of differentiation, proliferation, survival and migration. To achieve this aim, PAX3 expression was assessed in various tissue samples, including normal skin, naevi and melanoma (in situ, invasive, systemic and lymph node metastases). PAX3 expression across the variety of samples was analysed by immunohistochemistry, and by quantitative RT‐PCR. To characterise PAX3‐expressing cells, we initially performed co‐expression analysis of PAX3 with a known melanocytic marker MITF to confirm that PAX3‐ positive cells wer...
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