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Expression of the gene for the multidrug resistance-associated protein in human prostate tissue
Authors:Bernhard Schummer  Michael Siegsmund  Anette Steidler  Lira Toktomambetova  Kai-Uwe Köhrmann  Peter Alken
Affiliation:(1) Institute of Pharmacology and Toxicology, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Maybachstrasse 14–16, D-68169 Mannheim, Germany e-mail: schummer@rumms.uni-mannheim.de Tel.: 49 621 331067; Fax: 49 621 377601, DE;(2) Department of Urology, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany, DE
Abstract:To characterize the clinical relevance of MRP gene in the chemoresistance of prostate carcinomas we determined the multidrug resistance-associated protein (MRP) expression in 30 samples from organ-confined prostate carcinoma, 9 samples from adjacent normal tissue and 4 hormone unresponsive cancers. The measurement of MRP expression was carried out by reverse transcription polymerase chain reaction (RT-PCR) in combination with capillary electrophoresis. Incorporated fluorescence-labeled primers were disclosed by a laser-operated fluorescence detection module. MRP expression was quantified by integration of the peak area and correlated to the ubiquitously expressed beta2 microglobulin. As positive control served the adriamycin-resistant HL60-ADR cell line, which overexpresses MRP. MRP expression was found in all samples. All samples showed a lower MRP/beta2 ratio than HL60-ADR cells. The expression of the MRP gene was 30% higher in organ-confined tumors than in hormone-unresponsive anaplastic tumors. Normal tissue showed the same MRP mRNA level as the adriamycin-sensitive HL60 cells. A higher tumor stage correlated with an increase of MRP expression (> factor 2), whereas G3 tumors displayed a MRP expression 30% lower than in G2 tumors. The small alterations indicate that MRP expression seems not be involved in the chemoresistance of prostate carcinomas.
Keywords:Prostate carcinoma  Multidrug resistance  MRP gene  Multidrug resistance-associated protein
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