Use this URL to cite or link to this record in EThOS:
Title: Cellular fitness in response to oncogenic Kras
Author: Caldwell, M. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Here it is shown that the sequences that occurs during the development of pancreatic ductal adenocarcinoma is balanced by an equally abundant proliferative rate, suggesting that small perturbations that promote or impede proliferation may determine the rate of tumour progression. Furthermore, engagement of the MAP kinase pathway corresponds to enhanced cellular proliferation in pancreatic preneoplasms, providing a mechanistic basis for senescence avoidance. A p53-dependent cell autonomous barrier exists, but the complexity of this process is currently underappreciated as cellular fitness in pancreatic preneoplasms is governed by a multitude of parameters in vivo. In addition to the requisite genetic alterations, specific cellular behaviours must be during tumourigenesis and it is these behaviours that are ultimately representative of the pathological nature of the disease. Understanding how each genetic alteration directly influences cellular behaviours and the mechanisms that enable this has provided insight into the earliest stages of tumour development, prior to actual derangement of phenotypically wild type cells. This thesis seeks to demonstrate what the earliest behavioural changes are in response to endogenous expression of oncogenic Kras and how those acute responses enable extrapolation into eventual tumourigenesis or lack thereof. Based upon these results, we propose that pancreatic ductal cells are the likely cell of origin for ductal pancreatic cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available