Date of Award

2011

Degree Type

Thesis

Degree Name

Doctor of Philosophy

School

School of Exercise and Health Sciences

Faculty

Computing, Health and Science

First Advisor

Dr Melanie Ziman

Abstract

Background: Cutaneous melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 is critical for the proper development of neural crest lineages including melanocytes. Melanocytic cells show continued PAX3 expression from melanoblast formation in the neural crest to their differentiation into melanocytes. While many studies clarify the importance of PAX3 in embryonic development of melanocytes, less well understood, and more perplexing, is the continued PAX3 expression in adult skin melanocytes. By contrast PAX3 is frequently found in melanomas and naevi, and its expression correlates with melanoma staging. In this study we explore the multiple roles of PAX3 in melanocyte genesis and melanoma progression. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during embryonic development, it is not clear if these same functions are maintained in adult melanocytes or melanoma cells. Drawing on evidence from development, we propose here a more encompassing theory that PAX3 is a key regulator of the myriad steps in melanocytic cell determination and function. We discuss the possibility that these roles may be accomplished by differential association with cofactors, via alternate transcripts or posttranslational protein modification(s). Moreover, we consider its possible roles in melanoma and provide a comprehensive consideration of the significance of PAX3 expression in melanoma.

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