Identification of signalling pathways regulating TBX2 gene expression and its target genes

Doctoral Thesis


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University of Cape Town

Members of the T-box family of transcription factors provide an important link between development and cancer. T-box factors play critical roles in embryonic development and results from recent studies suggest that they function in controlling cell cycle progression and also in the genesis of cancer. Importantly, the T-box factors Tbx2 and Tbx3 are overexpressed in several cancers including melanoma, small cell lung carcinoma, breast, pancreatic, liver and bladder cancers and can suppress senescence, a cellular process which serves as a barrier to cancer development. However, the precise role of most T-box factors is poorly defined, in part, because their target genes are still poorly characterised and very little is known of the signalling pathways that regulate their expression and activity. The broad aim of this study was therefore to contribute towards the identification of Tbx2 target genes as well as to identify signalling pathways that regulate TBX2 expression. The specific aims were thus to (1) investigate the regulation of type1 collagen gene expression by Tbx2; (2) clone the human TBX2 regulatory region and to identify cis-acting elements involved in the basal transcription of the TBX2 gene and (3) investigate the regulation of TBX2 gene expression by signalling pathways.

Includes abstract.

Includes bibliographical references (leaves 83-97).