Proteomic changes in renal cancer and co-ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect
Richard D. Unwin
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorRachel A. Craven
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorPatricia Harnden
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorSarah Hanrahan
Cancer Research UK Protein Analysis Laboratory, London Research Institute, London, UK
Search for more papers by this authorNick Totty
Cancer Research UK Protein Analysis Laboratory, London Research Institute, London, UK
Search for more papers by this authorMargaret Knowles
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorIan Eardley
Department of Urology, St. James's University Hospital, Leeds, UK
Search for more papers by this authorPeter J. Selby
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorCorresponding Author
Rosamonde E. Banks
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Cancer Research UK Clinical Unit, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK Fax: +44-113-2429886===Search for more papers by this authorRichard D. Unwin
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorRachel A. Craven
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorPatricia Harnden
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorSarah Hanrahan
Cancer Research UK Protein Analysis Laboratory, London Research Institute, London, UK
Search for more papers by this authorNick Totty
Cancer Research UK Protein Analysis Laboratory, London Research Institute, London, UK
Search for more papers by this authorMargaret Knowles
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorIan Eardley
Department of Urology, St. James's University Hospital, Leeds, UK
Search for more papers by this authorPeter J. Selby
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Search for more papers by this authorCorresponding Author
Rosamonde E. Banks
Cancer Research UK Clinical Unit, St. James's University Hospital, Leeds, UK
Cancer Research UK Clinical Unit, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK Fax: +44-113-2429886===Search for more papers by this authorAbstract
Renal cell carcinoma (RCC) is the tenth most common cancer although the incidence is increasing. The main clinical problems stem from the relatively late presentation of many patients due to the often asymptomatic nature of the illness, and the relative insensitivity of metastatic disease to conventional chemotherapy and radiotherapy. Despite increasing knowledge of some of the genetic changes underlying sporadic renal cancer such as those involving the Von Hippel Lindau (VHL) gene, many of the underlying pathophysiological changes are ill-defined and there remains a need for the identification of disease markers for use in diagnosis and prognosis or as potential therapeutic targets. This study has used a proteomic approach, based on two-dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of conventional RCC tissue with patient-matched normal kidney cortex. Sequencing of 32 protein spots with significantly increased expression in RCC samples (≥ 4/6 patients) and 41 proteins whose levels decreased (6/6 patients) confirmed several previously known RCC-associated changes such as increases in Mn-superoxide dismutase, lactate dehydrogenase-A, aldolase A and C, pyruvate kinase M2, and thymidine phosphorylase. Additionally, several previously unknown changes were identified, including increased expression of three members of the annexin family and increased levels of the actin depolymerisation factor cofilin. The Warburg effect was also demonstrated with the identification of increases in proteins involved in the majority of steps in the glycolytic pathway and decreases in the gluconeogenic reactions, together with a parallel decrease in several mitochondrial enzymes. A number of the alterations seen were further confirmed in additional samples by immunohistochemistry, Western blotting, and laser capture microdissection.
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Citing Literature
Special Issue:SPS Proceedings 2nd Annual Congress Lausanne, 3–5 December 2002
August 2003
Pages 1620-1632