Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma

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dc.contributor.advisor Barry, Orla P. en
dc.contributor.advisor Fanning, Liam J. en O'Callaghan, Carol 2015-11-23T09:43:24Z 2015-11-23T09:43:24Z 2015 2015
dc.identifier.citation O'Callaghan, C. 2015. Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma. PhD Thesis, University College Cork. en
dc.identifier.endpage 292
dc.description.abstract Oesophageal cancer is an aggressive malignancy which is resistant to conventional therapy and has a poor prognosis. A greater understanding of the underlying molecular biology of oesophageal cancer and the identification of novel targets is necessary for the future treatment of this disease. This thesis focuses specifically on the ill-defined and understudied p38δ mitogen-activated protein kinase (MAPK) and its function(s) in oesophageal squamous cell carcinoma (OESCC). In contrast to the three other p38 isoforms (p38α, -β and –γ which have to-date been relatively well-studied), p38δ MAPK signalling is poorly understood. Thus, this research elucidates some of the role(s) played by p38δ MAPK in cancer progression. This work outlines how loss of p38δ MAPK expression confers greater tumourigenicity in oesophageal cancer. Restoration of p38δ MAPK expression, however, has anti-proliferative and anti-migratory effects and decreases OESCC capacity for anchorageindependent growth. Using a novel application of an enzyme-substrate fusion approach, the effect of phosphorylated p38δ (p-p38δ) MAPK expression is also considered. The work goes onto describe the effect(s) of p38δ MAPK status on the chemosensitivity of OESCC to conventional cisplatin and 5-fluorouracil (CF) versus the effectiveness of doxorubicin, cisplatin and 5-fluorouracil (ACF). ACF treatment of p38δ MAPK-negative OESCC results in decreased proliferation, migration and recovery, and increased apoptosis when compared with CF treatment. This thesis examines the potential mechanisms by which p38δ MAPK expression is lost in OESCC and identifies epigenetic regulation as the probable cause of differential p38δ MAPK expression. Also analysed is the role p38δ MAPK and p-p38δ MAPK play in the cell cycle. In summary, this research identifies p38δ MAPK as a possible molecular target and a potential predictor of response to chemotherapy in OESCC patients. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2015, Carol O'Callaghan. en
dc.rights.uri en
dc.subject Cancer en
dc.subject Oesophageal en
dc.subject p38 en
dc.subject MAPK en
dc.title Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text available en No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Health Research Board en
dc.description.status Not peer reviewed en Medicine en Pharmacology and Therapeutics en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
dc.internal.conferring Summer Conferring 2015

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© 2015, Carol O'Callaghan. Except where otherwise noted, this item's license is described as © 2015, Carol O'Callaghan.
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