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.
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.
Craven
Rachel A
RA
Cancer Research UK Clinical Centre, St. James's University Hospital, Beckett Street, Leeds, UK.
Hanrahan
Sarah
S
Totty
Nick
N
Harnden
Patricia
P
Stanley
Anthea J
AJ
Maher
Eamonn R
ER
Harris
Adrian L
AL
Trimble
William S
WS
Selby
Peter J
PJ
Banks
Rosamonde E
RE
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*
D020543:Proteome; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010744:Phosphoric Monoester Hydrolases; C497446:VHL protein, human