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© 1990 Oxford University Press

research-article

Expression of glutathione S-transferases in normal gastric mucosa and in gastric tumors

Wilbert H.M. Peters, Nicole G.M. Wormskamp and Ernst Thies 1

Division of Gastrointestinal and Liver Diseases, St Radboud Hospital PO Box 9101, 6500 HB Nijmegen, The Netherlands
1Department of Surgery, Medical University Lübeck FRG

Glutathione S-transferases from both normal gastric mucosa and its matched gastric tumors from 10 different patients were investigated. The transferases were purified and subsequenfly the isoenzyme composition was studied. Gtutathione S transferase (GST)-{pi} was present in all specimens in large amounts. Class {alpha} GSTs were present in 9 out of 10 normal specimens and in six tumors. In malignant tissue, expression of GSF-{pi} was increased at the expense of class {alpha} GST. In six patients, the ratio GST-{pi}/GST-{pi} was higher in tumorous versus normal tissue. On a Western blot, using a monoclonal antibody, GSt-µ was shown to be present in both normal and malignant tissue from four patients, the other six patients completely missed the enzyme in their gastric tissue. When present, GST-µ amounts to only a few per cent of total GST protein. GST-{pi} was quantified by densitometric analysis of Western blots, treated with a monoclonal antibody against GST-{pi}. Both total GST enzyme activity as well as the absohite amounts of GST-{pi} protein were significantly higher in the tumors, as compared to Its matched normal mucosa. The Importance of this overexpression of GST-{pi} was previously unknown. However, the frequent occurrence of this phenomenon in many refractory tumors, and as shown now also in gastric cancers, suggests a role for GST-{pi} in the mechanism of anti-cancer drug resistance.


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