title: Gene expression profiling in a renal cell carcinoma cell line: dissecting VHL and hypoxia-dependent pathways.
abstract: The von Hippel-Lindau tumor suppressor, pVHL, is a key player in one of the best characterized hypoxia signaling pathways, the VHL-hypoxia-inducible factor (VHL-HIF) pathway. To better understand the role of VHL in the hypoxia signaling pathways of tumor cells, we used serial analysis of gene expression (SAGE) to investigate hypoxia-regulated gene expression in renal carcinoma cells (786-0), with and without VHL. The gene expression profiles of the cancer cells were compared to SAGE profiles from normal renal proximal tubule cells grown under both normoxia and hypoxia. The data suggest that the role of VHL as a tumor suppressor may be more complex than previously thought. Further, the data reveal that renal carcinoma cells have evolved an alternative hypoxia signaling pathway(s) compared with normal renal cells. These alternative hypoxia pathways demonstrate VHL-dependent and VHL-independent regulation. The genes involved in such pathways include those with potential importance in the physiological and pathological regulation of tumor growth and angiogenesis. Some of the genes identified as showing overexpression in the cancer cells, particularly those encoding secreted or membrane-bound proteins, could be potential biomarkers for tumors or targets for rational therapeutics that are dependent on VHL status.
authors.affiliation: Genzyme Molecular Oncology, Framingham, MA 01701, USA.
authors.forename: Yide
authors.initials: Y
authors.lastname: Jiang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Keichii
authors.initials: K
authors.lastname: Kondo
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Klco
authors.forename: Thia B
authors.initials: TB
authors.lastname: St  Martin
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dufault
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Madden
authors.forename: William G
authors.initials: WG
authors.lastname: Kaelin
authors.forename: Mariana
authors.initials: M
authors.lastname: Nacht
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human