Expression, subcellular localisation and regulation of Programmed Cell Death Gene 4 (Pdcd4) in human pancreatic cells in response to hypoxia

Abstract

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, with a five year survival rate of less than five percent. New targets and more effective therapeutic intervention are required to improve diagnosis and prognosis for all patients with pancreatic cancer. Recent studies have established that the tumour suppressor protein Programmed Cell Death Gene 4 (PDCD4) plays a key role in the control of differentiation and neogenesis within the healthy adult pancreas. Pdcd4 was originally identified as a gene up-regulated during the process of apoptosis. However, recent data suggests a function for Pdcd4 as a tumour suppressor, making it a promising target for pancreatic cancer therapy. The present study utilised a novel model of tissue hypoxia, mimicking the oxygen-deprived core of cancerous tumours which is often resistant to conventional chemotherapeutic drugs and which is likely to lead to secondary tumour formation or metastases, especially in pancreatic cancer. Understanding how Pdcd4 regulates pancreatic cell fate, both in healthy pancreatic cells and in conditions of tissue hypoxia, may well arm us with a new weapon in our fight for more effective therapeutic intervention in the treatment and prevention of pancreatic cancer.

Date of Award	Oct 2014
Original language	English
Awarding Institution	University of Brighton