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© 1990 Oxford University Press

other

Decreased expression of the glutathione S-transferases alpha and pi genes in human renal cell carcinoma

Antje Klöne, Uwe Weidner, Rolf Hußnätter, Jonathan Harris 1, David Meyer 1, Stephan Peter 2 3, Brian Ketterer 1 and Helmut Sies 4

Institut für Physiologische Chemie 1, Universitä Düsseldorf Moorenstrasse 5, Düsseldorf, FRG
1Department of Biochemistry, University College and Middlesex School of Medicine Windeyer Building, Cleveland Street, London, UK
2Urologische Klinik, Universität Düsseldorf Moorenstrasse 5, Düsseldorf, FRG

3Present address: Städtische Kliniken Darmstadt, Grafenstrasse 9, D-6100 Darmstadt, FRG

4To whom correspondence should be addressed

Using the polymerase chain reaction (PCR), a human kidney glutathione S-transferase (GST) alpha cDNA clone (GST {alpha} 12 K) was synthesized; it is identical to a known liver GST alpha cDNA clone except for one base change (G -> A), indicating that an alpha class gene expressed in human kidney is similar to one expressed in human liver. Comparisons were made in the expression of GST alpha and GST pi between renal cell carcinoma and adjacent non-Neoplastic tissue. Messenger RNA expression in 30 cases was determined by Northern blotting, and GST protein from nine of these cases was analyzed by HPLC. The GST alpha gene products were expressed at near-zeri levels. The GST pi gene product was the predominant GST in tumors, but was decreased in absolute amount compared with control tissue, the tumor/control ratios for the GST pi gene obtained by Northern blots and HPLC analysis being 0.50 ± 0.07 and 0.36 ± 0.07 respectively. The resulting pattern in renal cell carcinoma therefore shows a predominance of GST pi. Since it is assumed that renal cell carcinoma derives from the proximal tubular epithelial cells which are high in GST alpha, this implies a dedifferentation in the GST expression pattern.


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