Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.801334
Title: The identification and functional characterisation of TEX19 in human cancer cells
Author: Alqahtani, Leena
Awarding Body: Bangor University
Current Institution: Bangor University
Date of Award: 2020
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Abstract:
Cancer Testis Antigen (CTA) genes are a group of genes that are expressed in male germ cells in the healthy adult testis and not healthy somatic tissue, but are also expressed in a range of cancers. This study describes the detection of testis-expressed 19 (TEX19), as a novel human CTA gene, the product of which is proposed to be a therapeutic drug target. The study presents an analysis of the gene expression and protein localisation of TEX19 and provides insight into the way it may function in various cancer cells. TEX19 has been reported as a potential oncogenic driver which may be involved in the proliferation of cancer cells and the self-renewal of human cancer cells in vitro. It is therefore potentially capable of affecting clinical outcomes. The results of this study confirm that TEX19 is a CTA gene and that TEX19 protein has been detected in several kinds of cancers. The cellular localisation of TEX19 in cancer cells has been found to be both nuclear and cytoplasmic, which may indicate dynamic localisation. Co-localisation between TEX19 and H3K9ac in interphase nuclei was observed, suggesting a possible functional association. However, during mitosis (metaphase/anaphase), TEX19 appears to be excluded from the condensed chromatin, which further suggests that there is a functional association between TEX19 and chromatin. While the reasons for this are not clear at present, it may suggest that TEX19 functions to support a de-condensed chromatic state. In this study, we demonstrate that TEX19 appears to have a functional role in chromatin regulation in cancer cells, and that it might control histone acetylation (H3K9). Extending this, it was found that the siRNA depletion of TEX19 results in a significant reduction in H3K9ac. Additionally, siRNA depletion of TEX19 results in the appearance of a small number of aberrant mitotic events. Thus, a possible role of TEX19 in epigenetic control of chromatin and/or chromosome dynamics has also been demonstrated in this study. This research also shows that TEX19 plays a role in the regulation of chromatin in cancerous cells and influences the histone acetylation/deacetylation mechanism. These findings form the basis for an understanding of the functional role of TEX19 in cancerous cells and offer an opportunity to develop a TEX19-based therapy for cancer treatment.
Supervisor: Mcfarlane, Ramsay Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.801334  DOI: Not available
Keywords: Cell proliferation ; TEX19 ; Cancer Testis antigens (CTA)
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