New Perspectives on Melanoma_ The Role of PAX3

Itispossiblethatpax3controlsmaintenance19and survival

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Unformatted text preview: a rate of 3‐7% per annum [5,6]. Australia has the highest incidence of melanoma in the world, with Western Australia following closely behind Queensland [7]. Official reports from the Western Australia Cancer Registry for the year 2008 (http://www.health.wa.gov.au/wacr) rate melanoma as the third most common cancer overall (with 1082 new cases reported in 2008). It is the most common cancer in young males and the second most common type in young females (age 15‐39). The 5‐year survival rate for early stage melanoma patients is high (around 95%), however, the fifteen year survival rate for some of those patients drops to around 40%, and for advanced stage patients 5‐year survival is less that 20% [8,9]. It is important therefore to understand in detail the mechanisms driving melanoma development and progression. PAX3 transcription factor PAX3 (paired box 3) is a paired box transcription factor, expressed during early embryonic development in cells of neural crest origin, the cells which give rise to skin melanocytes. In fact, PAX3 plays a key role in specification of melanoblasts and in maintenance of their stem‐like/undifferentiated state. PAX3 also regulates proliferation and migration to their final location in the skin, where they terminally differentiate into melanocytes [10‐15]. PAX3 regulates these processes through direct activation (or repression) of its downstream target genes which control these pathways. 1 Chapter I – Thesis Overview While PAX3 expression and its roles during embryonic development have been well described, its persistent expression in normal adult epidermal melanocytes has been confirmed only recently [16‐18], and the precise role of PAX3 in these cells is less well understood. It is possible that PAX3 controls maintenance [19] and survival of melanocyte stem cells, required for continuous repopulation of skin melanocytes, and facilitates their proper migration. It might also regulate survival of differentiated epidermal melanocytes and their expansion/ proliferation in response to sun exposure [20]. Notably, PAX3 is high...
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