Cell Cycle Deregulation in Pre-neoplasia: Case Study of Barrett’s Oesophagus
Most solid tumours develop through a pre-invasive stage referred to as intra-epithelial neoplasia (IEN). The lag time between development of IEN and progression to fully fledged cancer would allow for chemoprevention or therapeutic interventions; however in most cases, IEN remains undetected and the exact mechanisms for progression remain unknown. Barrett’s oesophagus, the premalignant stage of oesophageal adenocarcinoma, is the perfect model to study IEN since the oesophagus is readily accessible by endoscopy and allows for temporal follow-up of patients. Like most IEN, Barrett’s oesophagus and associated dysplasia are characterized by an increase in proliferation and the expansion of the proliferative compartment. These features have been associated with an increased risk of progression to cancer. There is evidence of dysregulation of the G1/S and G2/M checkpoints which may be caused by an accumulation of abnormally expressed growth factors and oncogenes. Furthermore, the abnormally high level of duodeno-gastro-oesophageal acid reflux bathing the distal oesophagus contributes further to increasing proliferation. The real challenge for future research will be to identify causal events and to develop better diagnostic methods and therapeutic options.
KeywordsAcid Reflux Oesophageal Adenocarcinoma Proliferative Compartment Autocrine Stimulation Luminal Factor
- BSG (2005) Guidelines for the diagnosis and management of Barrett’s columnar-lined oesophagus. http://www.bsg.org.uk
- Morgan C, Alazawi W, Sirieix P, Freeman N, Coleman N, Fitzgerald RC (2003) Immediate and early gene response to in vitro acid exposure in a Barrett’s adenocarcinoma cell line. Gut 52(Suppl 1): A44.Google Scholar