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

M Craig Caldwell; Colleen Hough; Stefanie Fürer; W Marston Linehan; Patrice J Morin; Myriam Gorospe

doi:10.1038/sj.onc.1205140

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

Oncogene. 2002 Jan 31;21(6):929-36. doi: 10.1038/sj.onc.1205140.

Authors

M Craig Caldwell¹, Colleen Hough, Stefanie Fürer, W Marston Linehan, Patrice J Morin, Myriam Gorospe

Affiliation

¹ Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

PMID: 11840338
DOI: 10.1038/sj.onc.1205140

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 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.

MeSH terms

Blotting, Northern
Blotting, Western
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / metabolism
Carcinoma, Renal Cell / pathology
Computer Systems
Drug Resistance / genetics
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic / genetics
Gene Expression Regulation, Neoplastic / physiology*
Gene Library
Humans
Kidney Neoplasms / genetics*
Kidney Neoplasms / metabolism
Kidney Neoplasms / pathology
Ligases / deficiency
Ligases / genetics
Ligases / physiology*
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Polymerase Chain Reaction
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
RNA, Neoplasm / biosynthesis
RNA, Neoplasm / genetics
Recombinant Fusion Proteins / physiology
Transfection
Tumor Cells, Cultured / drug effects
Tumor Cells, Cultured / metabolism
Tumor Necrosis Factor-alpha / toxicity*
Tumor Suppressor Proteins*
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein

Substances

Neoplasm Proteins
RNA, Messenger
RNA, Neoplasm
Recombinant Fusion Proteins
Tumor Necrosis Factor-alpha
Tumor Suppressor Proteins
Ubiquitin-Protein Ligases
Von Hippel-Lindau Tumor Suppressor Protein
Ligases
VHL protein, human