Expression of the gene for the multidrug resistance-associated protein in human prostate tissue.
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.
Schummer
B
B
Institute of Pharmacology and Toxicology, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany. schummer@rumms.uni-mannheim.de
Siegsmund
M
M
Steidler
A
A
Toktomambetova
L
L
Köhrmann
K U
KU
Alken
P
P
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D017931:DNA Primers; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm