title: Impact of cisplatin administration on protein expression levels in renal cell carcinoma: a proteomic analysis.
abstract: Renal cell carcinoma (RCC) is the most common renal neoplasm in adults. Considering that chemoresistance is a typical feature of RCC, every effort should be made in order to identify mechanisms of drug resistance. We used two-dimensional gel electrophoresis and mass spectrometry to study changes in protein expression levels that occur in primary resistant LN78 RCC cells when treated with therapeutic concentrations of cisplatin. Expression differences of selected proteins were confirmed by immunoblot. Up-regulation of heat-shock proteins can block apoptosis indirectly by altered protein folding and by direct interaction with apoptosis regulatory proteins. Cyclophilin A and stratifin can modify cell cycle control and enable tumor cells to escape and further proliferate despite DNA damage caused by cisplatin. Increased activity of glycolytic enzymes reflect metabolic adaptations to increased energy requirements as well as converting to alternative energy sources because of cisplatin-induced disturbed mitochondrial oxidation. Changes in cytoskeletal proteins may change the handling of cisplatin by altering transport and increasing cellular efflux of the drug. Repression of vimentin and disturbance of antioxidative mechanisms may represent vulnerable points in tumor cellular defense against cisplatin. The involvement of these proteins in cisplatin resistance and their potential as therapeutic targets requires further evaluation.
authors.affiliation: Department of Nephrology and Rheumatology, Georg-August-University Goettingen, Germany. vaskorad@googlemail.com
authors.forename: Radovan
authors.initials: R
authors.lastname: Vasko
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Mueller
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: von Jaschke
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Asif
authors.forename: Hassan
authors.initials: H
authors.lastname: Dihazi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D013058:Mass Spectrometry; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D020543:Proteome; D002945:Cisplatin