title: Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma and their effects on metabolism.
abstract: During the last decade the knowledge about the molecular mechanisms of the cellular adaption to hypoxia and the function of the "von Hippel Lindau" (VHL) protein in renal cell carcinoma (RCC) has increased, but there exists little information about the overlap and differences in gene/protein expression of both processes. Therefore the aim of this study was to dissect VHL- and hypoxia-regulated alterations in the metabolism of human RCC using ome-based strategies. The effect of the VHL- and hypoxia-regulated altered gene/protein expression pattern on the cellular metabolism was analyzed by determination of glucose uptake, lactate secretion, extracellular pH, lactate dehydrogenase activity, amino acid content and ATP levels. By employing VHL-/VHL(+) RCC cells cultured under normoxic and hypoxic conditions, VHL-dependent, HIF-dependent as well as VHL-/HIF-independent alterations in the gene and protein expression patterns were identified and further validated in other RCC cell lines. The genes/proteins differentially expressed under these distinct conditions were mainly involved in the cellular metabolism, which was accompanied by an altered metabolism as well as changes in the abundance of amino acids in VHL-deficient cells. In conclusion, the study reveals similarities, but also differences in the genes and proteins controlled by VHL functionality and hypoxia thereby demonstrating differences in the metabolic switch of RCC under these conditions.
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leisz
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schulz
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Erb
authors.affiliation: Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Oefner
authors.affiliation: Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Dettmer
authors.affiliation: Department of Internal Medicine 5, University of Erlangen, 91054 Erlangen, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mougiakakos
authors.affiliation: Sidra Medical and Research Center, PO Box 26999, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Sidra Medical and Research Center, PO Box 26999, Doha, Qatar.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Stehle
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D014162:Transfection; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D005947:Glucose
keywords: aerobic glycolysis; cell metabolism; hypoxia; renal cell carcinoma; von Hippel Lindau gene