Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFα cytotoxicity

被引:32
作者
Caldwell, MC
Hough, C
Fürer, S
Linehan, WM
Morin, PJ
Gorospe, M
机构
[1] NIA, GRC, IRP,NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA
[2] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA
关键词
VHL; SAGE; renal cell carcinoma; gene expression; TNF alpha;
D O I
10.1038/sj.onc.1205140
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have used serial analysis of gene expression (SAGE) to investigate the influence of the von Hippel-Lindau (VHL) gene on global gene expression profiles. SAGE libraries were prepared from renal cell carcinoma (RCC) lines that either lack (parental) or express wild-type VHL (wtVHL). Comparison of these libraries revealed some differentially expressed genes (Glut-1, for example) that were known to be influenced by VHL, but the majority of genes had not previously been reported to be affected by the cell's VHL status. The identification of several genes involved in TNFalpha-mediated events prompted us to compare the sensitivity of cells with different VHL status in TNFalpha cytotoxicity assays. Strikingly, VHL-deficient cells were much more resistant to the toxic influence of TNFalpha. We propose that VHL-dependent sensitization of RCC cells to TNFalpha-mediated killing may contribute to VHL's growth suppressive function.
引用
收藏
页码:929 / 936
页数:8
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