The role of the transcription factor TBX2 in breast cancer and melanoma and its regulation by the UV-induced DNA damage pathway.

Includes abstract. ; Includes bibliographical references. ; T-box genes constitute an ancient family of developmentally important transcription factors that have gained prominence in cancer biology. For example, endogenous TBX2 is overexpressed in a growing list of cancers and when ectopically overexpressed it can bypass senescence and the tetraploidy checkpoints that protect against cancer. When the current study was initiated it was unclear as to whether the endogenous overexpression of TBX2 was a cause or consequence of the oncogenic process and whether it may be a suitable anti-cancer drug target. The objectives of this study were therefore (1) to explore the role of increased TBX2 levels in melanomagenesis by assessing the effect of knocking it down in melanoma cell lines, (2) to determine the mechanism by which TBX2 is upregulated by the UV-induced DNA damage pathway in melanoma cells and (3) to verify whether TBX2 is a suitable drug target by assessing the cellular sensitivity of control and TBX2-depleted cells in response to the chemotherapeutic drug cisplatin.