Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science (Human Biology)

School

School of Medical Sciences

Faculty

Health, Engineering and Science

First Advisor

Professor Mel Ziman

Second Advisor

Dr. Sandra Medic

Abstract

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies that PAX3 may be involved in such regulatory pathways in all of these cell types including melanoma. Melanoma is a notoriously aggressive and drug resistant form of skin cancer. Research into the role of PAX3 in melanoma could provide novel treatment options for targeted therapies aimed at PAX3 or its regulatory pathways.

Therefore, in this study, the expression profile of PAX3 alternate transcripts was compared in normal melanocytes and melanoma cells. Moreover, differences in post-translational modifications between these cell types were assessed, as were changes in downstream target genes. This research further clarifies the role of PAX3 in melanoma and details the differences in its role here, relative to that in melanocytes.

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