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Title: The functional characterisation of TEX19 in human cancer cells and stem cells to explore clinical potential
Author: Hazazi, Ali Mohammed
ISNI:       0000 0004 6352 4143
Awarding Body: Prifysgol Bangor University
Current Institution: Bangor University
Date of Award: 2017
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The study of human embryonic stem cells (hESCs) and cancer cells in vitro is useful for exploring the behaviour of cells employed in the development of regenerative medicine and clinical applications. Testis expressed 19 (TEX19) is a specific human germ/stem cell gene identified as cancer testis antigen (CTA) gene that has recently emerged as a potential therapeutic drug target. CTA gene expression is normally restricted to human germline tissues, and these genes are activated in a wide range of tumour cells and cancer stem cells, hence, their intrinsic characteristics mark them as excellent potential cancer-specific biomarkers and promising drug/immunotherapeutic targets. CTA gene expression has been linked with stemness, but their function in stem cells has not been fully explored. The findings of this study confirmed that TEX19 is a CTA gene that is expressed in the testes and in numerous cancer types. Additionally it was demonstrated that human TEX19 is expressed in hESCs and Induced pluripotent stem cells (iPSCs). TEX19 has dual cellular localisation, namely in the nucleus/cytoplasm, and may have a dynamic localisation in cancer cells. TEX19 is demonstrated to be a candidate oncogenic driver with a potential function in enhancing cancer cell proliferation and the self-renewal of human cancer cells in vitro; hence, it could contribute to influencing clinical outcomes. Furthermore, evidence is provided that TEX19 potentially acts as a transcriptional regulator by altering the transcript levels of multiple genes in distinct human cancer cells. TEX19 also regulates the mRNA levels of crucial stem cell marker genes in hESCs, NANOG in particular. These data also show that the loss of pluripotency in different human embryonic stem (hES) cell lines upon differentiation modifies the TEX19 mRNA levels. Finally, the study demonstrates that TEX19 is required to control transposable element (TE) transcript levels in cancer cells and hESCs. Taking these findings together, the observations from cancer cells and hESCs suggest that TEX19 is a stemness regulatory factor with possible application as a cancer biomarker/therapeutic target.
Supervisor: Mcfarlane, Ramsay ; Wakeman, Jane Sponsor: Security Forces Hospital
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available