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

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Abstract
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 TNFα-mediated events prompted us to compare the sensitivity of cells with different VHL status in TNFα cytotoxicity assays. Strikingly, VHL-deficient cells were much more resistant to the toxic influence of TNFα. We propose that VHL-dependent sensitization of RCC cells to TNFα-mediated killing may contribute to VHL's growth suppressive function.