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Expression of glutathione S-transferases in normal gastric mucosa and in gastric tumors
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)-
was present in all specimens in large amounts. Class
GSTs were present in 9 out of 10 normal specimens and in six tumors. In malignant tissue, expression of GSF-
was increased at the expense of class
GST. In six patients, the ratio GST-
/GST-
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-
was quantified by densitometric analysis of Western blots, treated with a monoclonal antibody against GST-
. Both total GST enzyme activity as well as the absohite amounts of GST-
protein were significantly higher in the tumors, as compared to Its matched normal mucosa. The Importance of this overexpression of GST-
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-
in the mechanism of anti-cancer drug resistance.
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