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 subsequently the isoenzyme composition was studied. Glutathione 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 GST-pi was increased at the expense of class alpha GST. In six patients, the ratio GST-pi/GST-alpha was higher in tumorous versus normal tissue. On a Western blot, using a monoclonal antibody, GST-mu 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-mu 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 absolute 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.
Division of Gastrointestinal and Liver Diseases, St Radboud Hospital, Nijmegen, The Netherlands.
W H
WH
Peters
N G
NG
Wormskamp
E
E
Thies
D000328:Adult; D000368:Aged; D003600:Cytosol / Q000201:enzymology; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology*; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013274:Stomach Neoplasms / Q000201:enzymology*
D007527:Isoenzymes; D005982:Glutathione Transferase