Expression of glutathione S-transferase theta class isoenzymes in human colorectal and gastric cancers.
Glutathione S-transferases (GSTs) are a superfamily of detoxification enzymes, which play an important role in the protection of tissues against potentially harmful compounds. In humans, two theta class isoenzymes, GSTT1-1 and GSTT2-2, have been described so far. Both enzymes were claimed to have an important role in human carcinogenesis. In colorectal and gastric tissues, the expression of the other isoenzymes changes after malignant transformation. No data on the expression levels of the theta isoenzymes in these tissues are available. The aim of this study was to determine the protein levels of the two theta class isoenzymes in human colorectal and gastric cancers and paired normal tissue. Cytosolic fractions of normal and matched tumor tissue samples from 20 patients with colorectal or gastric adenocarcinomas were analyzed on immunoblots using specific antibodies against GSTT1-1 and GSTT2-2, respectively. In addition paraffin-embedded sections of these tissues were examined immunohistochemically for GSTT1-1 expression. In both types of tissue, theta class isoenzymes were highly expressed. Expression of GSTT1-1 was higher in gastric than in colorectal tissues. The GSTT2-2 levels were comparable in both tissues. A great interindividual difference in expression was demonstrated. In colon, there was no change in the theta class isoenzyme levels after malignant transformation. Gastric tumors had significantly lower expression of both theta class isoenzymes compared with the normal mucosa. In colon, GSTT1-1 was expressed in the enterocytes and goblet cells. In gastric tissues, staining was seen in upper and deeper mucous cells, chief cells and, to a lesser extent, in parietal cells. In both types of tumors, staining was seen in adenomatous cells. In conclusion, in both normal human colonic and gastric mucosa, GSTT1-1 and GSTT2-2 are present at high levels, whereas after malignant degeneration, expression is not influenced or is even downregulated.
de Bruin
W C
WC
Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands.
Wagenmans
M J
MJ
Board
P G
PG
Peters
W H
WH
D000230:Adenocarcinoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012016:Reference Values; D013274:Stomach Neoplasms / Q000201:enzymology*
D009363:Neoplasm Proteins; C491107:GSTT2 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase