Differential expression of the multidrug resistance-related protein MRP1 in the histological compartments of nephroblastomas.
Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for prognostic markers, we investigated the expression of the multidrug resistance-related protein 1 (MRP1) in 32 nephroblastomas by means of immunohistochemistry. The immunohistochemical results were validated with a real-time RT-PCR technique. MRP1 expression was heterogeneous and predominantly found in the blastemal and epithelial compartments compared to the stromal elements of nephroblastomas. We found significant relationships of MRP1 expression to survival of patients and to expression of p53, HSP70, and LRP/MVP. The relationship between MRP1 and p53 expression is a clue that the transcriptional control of MRP1 by p53 reported for other tumor types may also take place in nephroblastomas. The correlation of MRP1 to other drug resistance genes, e.g. HSP70 and LRP/MVP in nephroblastomas indicates that the co-expression of different drug resistance genes may be under a common regulation of still unknown transcription factors.
Efferth
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Virtual Campus Rhineland-Palatinate, P.O. Box 4380, G-55033 Mainz, Germany. efferth@vcrp.de
Thelen
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Schulten
H G
HG
Bode
M E
ME
Granzen
B
B
Beniers
A J
AJ
Mertens
R
R
Ringert
R H
RH
Gefeller
O
O
Jakse
G
G
Fuzesi
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D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics*; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D020394:Vault Ribonucleoprotein Particles; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000099187:Major Vault Protein
D018528:ATP-Binding Cassette Transporters; D018840:HSP70 Heat-Shock Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein