EXPRESSION OF GLUTATHIONE S-TRANSFERASES IN NORMAL GASTRIC-MUCOSA AND IN GASTRIC TUMORS

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)-π was present in all specimens in large amounts. Class α GSTs were present in 9 out of 10 normal specimens and in six tumors. In malignant tissue, expression of GSF-π was increased at the expense of class α GST. In six patients, the ratio GST-π/GST-π 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-π was quantified by densitometric analysis of Western blots, treated with a monoclonal antibody against GST-π. Both total GST enzyme activity as well as the absohite amounts of GST-π protein were significantly higher in the tumors, as compared to Its matched normal mucosa. The Importance of this overexpression of GST-π 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-π in the mechanism of anti-cancer drug resistance. © 1990 Oxford University Press.