New Perspectives on Melanoma_ The Role of PAX3

The logical assumption is that the roles

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Unformatted text preview: expression in adult epidermal melanocytes has been uncertain, with only a few studies reporting PAX3 expression in human melanocytes [16,17]. It has been suggested that TGFβ‐mediated PAX3 upregulation under increased UV exposure induces melanocyte proliferation [20]. Similarly, ectopic expression of PAX3 promotes growth, proliferation and migration of transfected melanocytes [163]. Taken together, the results highlight the importance of PAX3 in melanocytes, and justify the need to identify the precise mechanism of its regulation, not just in melanocytes but also in melanoma. Normal skin melanocytes reside in a very dynamic microenvironment; on one side they are exposed to the outer macroenvironment, and on the inside to a continuum of cyclical changes. They have a close functional relationship with surrounding cells, regulated by cell‐cell cross talk, to maintain homeostasis. It is clear then that melanocytes are required to consistently maintain responsiveness to environmental cues. This includes cyclic melanocyte stem cell activation to proliferate giving rise to transient amplifying progeny cells that 24 Chapter I – Thesis Overview migrate in the growing hair towards the matrix of the bulb, where the mature melanocytes will commence melanogenesis. Different signalling networks exist in the niche (Wnt protected area) to that in the growing hair follicle [118,149,150]. Once the progenitor cells exit the niche, further signals determine their migration and maturation. So here, melanocyte stem cell progeny respond to endogenous/intrinsic/ innate cycles dictated by the environment. By contrast, epidermal melanocyte response is driven by exogenous/external signals, predominantly UV exposure (reviewed in [164]. As a result, melanocytes respond, by increasing in number and with increased melanogenesis [20]. It is not clear however, whether increases in epidermal melanocyte numbers result from their proliferation or from the activation and migration of bulge melanocy...
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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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