Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFα cytotoxicity
Serial analysis of gene expression in renal carcinoma cells reveals VHL-dependent sensitivity to TNFα cytotoxicity
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DOI：
10.1038/sj.onc.1205140
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发表时间：
2002-01-31
期刊：
影响因子：
8
通讯作者：
Gorospe, M
中科院分区：
文献类型：
--
作者：
Caldwell, MC;Hough, C;Gorospe, M
我们使用基因表达系列分析（SAGE）来研究von Hippel-Lindau（VHL）基因对全球基因表达谱的影响。SAGE文库由缺乏（亲本）或表达野生型VHL（wtVHL）的肾细胞癌（RCC）系制备。这些文库的比较揭示了一些已知受VHL影响的差异表达基因（例如Glut-1），但大多数基因以前没有报道过受细胞VHL状态的影响。参与TNF α介导事件的几个基因的鉴定促使我们在TNF α细胞毒性测定中比较具有不同VHL状态的细胞的敏感性。引人注目的是，VHL缺陷细胞对TNF α的毒性影响更具抵抗力。我们认为，VHL依赖性敏化RCC细胞TNFa介导的杀伤可能有助于VHL的生长抑制功能。
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.