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Title: Evaluation of the role of Epsins and Notch1 in oral carcinogenesis
Author: Ahmed, Halah Fawzi
ISNI:       0000 0004 7659 8037
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 2018
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There are around 300,000 new oral cancers diagnosed worldwide every year, the majority are oral squamous cell carcinomas (OSCCs). Most patients present with late stage disease and have a poor prognosis. However, some OSCCs develop within oral potentially malignant disorders and early stage OSCC is curable. Consequently, early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression, however, none have been translated into clinical practice. The aim was to investigate the role of the endocytic adaptor proteins called Epsins (Epsin1, 2, 3) and the transmembrane protein, Notch1, in oral carcinogenesis and explore their potential in diagnostic utility. A panel of nine OSCC cell lines and an immortalized normal oral keratinocyte cell line were cultured. qRT-PCR, Western blot and immunocytochemistry were used to assess the expression levels of Epsins and Notch1. Epsin1 was detected at both the RNA and protein levels in all the cell lines tested, while Epsin2 was not detectable. Epsin3 and Notch1 showed differential expression across the cell lines. Reduced expression of Epsin3 through siRNA did not affect the expression of Notch1. In contrast, overexpression of Epsin3 resulted in a significant reduction of Notch1 expression. Immunohistochemical analysis of tissue samples from a well characterised cohort of patients revealed that Epsin3 expression was higher in oral epithelial dysplasia and OSCC by comparison with normal epithelium. In parallel, Notch1 was generally lower in the dysplasia and OSCC samples, supporting the in vitro data and the hypothesis that Notch1 has a tumour-suppressor function. The results indicate that Epsin3 is dysregulated in OSCC and has potential to be used as a biomarker in oral epithelial dysplasia. Notch signaling is downregulated in OSCC, possibly through an Epsin3 induced de-activation pathway.
Supervisor: Not available Sponsor: Iraqi Ministry of Higher Education and Scientific Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available