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

被引:51
作者
Craven, Rachel A.
Hanrahan, Sarah
Totty, Nick
Harnden, Patricia
Stanley, Anthea J.
Maher, Eamonn R.
Harris, Adrian L.
Trimble, William S.
Selby, Peter J.
Banks, Rosamonde E.
机构
[1] St James Univ Hosp, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England
[2] London Res Inst, Canc Res UK Prot Anal Lab, London, England
[3] Univ Birmingham, Canc Res UK Renal Mol Oncol Res Grp, Birmingham, W Midlands, England
[4] Univ Oxford, Weatherall Inst Mol Med, Canc Res UK Mol Oncol Labs, Oxford, England
[5] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada
[6] Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada
关键词
mitochondrial enzymes; renal cancer; septin; transfectants; von Hippel Lindau;
D O I
10.1002/pmic.200500811
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3880 / 3893
页数:14
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