title: Proteomic identification of a role for the von Hippel Lindau tumour suppressor in changes in the expression of mitochondrial proteins and septin 2 in renal cell carcinoma.
abstract: The von Hippel Lindau (VHL) tumour suppressor gene, VHL, plays a central role in development of sporadic conventional renal cell carcinomas (RCCs). Studying VHL function may, therefore, increase understanding of the pathogenesis of RCC and identify markers/therapeutic targets. Comparison of 2-DE protein profiles of VHL-defective RCC cells (UMRC2) transfected with control vector or wild-type VHL showed differences in 30 proteins, including several novel changes. One of the findings confirmed by Western blotting was up-regulation of the mitochondrial protein ubiquinol cytochrome c reductase complex core protein 2 following VHL transfection, a change that was also observed in two other cell line backgrounds. A marked decrease in expression of this and several other mitochondrial proteins was demonstrated in RCC tissues and using VHL-transfectants, several were shown to exhibit VHL-dependent regulation. Thus, VHL may contribute to the decreased mitochondrial function seen in RCC. A form of septin 2 down-regulated following VHL transfection was also identified. Septin 2 was up-regulated in 12/16 RCCs, while alteration of the form present was also observed in 1/3 tumours analysed. Thus, increased expression of septin 2 is a common event in RCC and protein modification may also alter septin 2 function in a subset of tumours.
authors.affiliation: Cancer Research UK Clinical Centre, St. James's University Hospital, Beckett Street, Leeds, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Craven
authors.forename: Sarah
authors.initials: S
authors.lastname: Hanrahan
authors.forename: Nick
authors.initials: N
authors.lastname: Totty
authors.forename: Patricia
authors.initials: P
authors.lastname: Harnden
authors.forename: Anthea J
authors.initials: AJ
authors.lastname: Stanley
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.forename: Rosamonde E
authors.initials: RE
authors.lastname: Banks
mesh_terms: D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D020543:Proteome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism / Q000502:physiology*
chemical_list: D020543:Proteome; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010744:Phosphoric Monoester Hydrolases; C497446:VHL protein, human