Date of Award

1-1-2005

Document Type

Thesis

Publisher

Edith Cowan University

Degree Name

Master of Science

Faculty

Faculty of Computing, Health and Science

First Supervisor

Dr M.R. Ziman

Abstract

This research investigated the repercussions of aberrant PAX3 re-expression in cutaneous malignant melanoma (CMM). The transcription, factor encoded by PAX is amongst the first expressed in the embryo, with a principal role in the development of the melanocytic lineage. We theorised that abnormal re-expression of PAX3, consistently observed in CMM as compared to normal melanocytes, is linked to progression of CMM. Previous studies have stated that expression profiles of PAX3 in CMM demonstrate predominant generation of a protein encoded by exons 1-9 (PAX3D) utilizing cryptic splice sites in post-transcriptional pre-mRNA splicing. By contrast, normal human skin demonstrates low level generation of PAX3C (encoded by exons 1-8). Using RT-PCR based techniques and immunohistochemistry, we present original evidence of Pax3c, Pax3d mRNA and protein expression in normal murine embryogenesis and melanogenesis, identifying a conserved role for the Pax3d protein in transcriptional regulation of the murine melanoblast. Furthermore, to identify a role for Pax3 in adult skin, we used a reliable time-scale for the strict coupling of melanogenesis to active hair regrowth; Pax3c and Pax3d expression profiles were assessed during depilation experiments which induced murine malanocytic stem cells to proliferate, migrate into the hair cortex and differentiate in order to produce melanin for new hair. Results indicate that strict temporal expression of Pax3d may be linked to either melanoblast proliferation or migration in early melanogenesis thus supporting a possible role for PAX3D in the tumourigenesis of CMM.

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