Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.664725
Title: Molecular and functional analysis of the tumour antigen T21
Author: Alshehri, B. M.
ISNI:       0000 0004 5365 389X
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2015
Availability of Full Text:
Access through EThOS:
Access through Institution:
Abstract:
Immunotherapy is a valuable approach to target tumour cells by stimulating the body’s adaptive immune system. To achieve this objective, it is important to identify and study antigens that are distinctively expressed in cancer and can be used effectively to initiate or enhance immune responses. T21 (Testis clone 21) was identified as a member of cancer/testis antigen (CTAs) family of proteins using a modified SEREX technique and can be considered a promising prostate-associated tumour antigen, shown to elicit a humoral immune response in prostate cancer patients. T21 has also been shown to be over-expressed in malignant glands of the prostate compared to benign glands and stroma at the mRNA level. Since T21 shares significant similarity with the Centrosomal Protein, CEP290, which has been implicated in several cilia associated syndromic disorders such as Joubert syndrome, it was necessary to determine similarities and differences in the expression and functionality of these two molecules to facilitate further studies on the role of T21 in prostate cancer tumourigenesis. As with the majority of identified cancer/testis antigens, the role of T21 in cancer remains undetermined. Therefore, investigations were initiated to understand the potential function of T21 in cancer cells. Next Generation Sequencing (NGS) data have been previously obtained following T21 knockdown/silencing in PC3 cells and the expression profiling of this data indicated that T21 function was related to several pathways involved in tumourigenesis. Genes that were either up or down regulated in the presence of T21 were validated by qRT-PCR and the results provided evidence that T21 may share functional activity these various genes and be implicated as a key driver of important signaling pathways. The up or down regulation of molecules associated with key signaling pathways was established from the NGS data and validated by qRT-PCR. The effect of T21 silencing on the associated MAPK pathways was further investigated by using proteome profiler arrays. The results indicated the potential role that T21 may play in cancer cell growth regulation and suggested that T21 is potentially a central player in the cancer process. Finally, the data presented here strongly supports the hypothesis of T21 having a significant role in the biology of malignant cells. This, together with its potential use in immunotherapy, that warrants further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.664725  DOI: Not available
Share: