Carcinogenesis, Vol. 20, No. 8, 1453-1458,
August 1999
© 1999 Oxford University Press
Cancer Biology |
Expression of glutathione S-transferase
class isoenzymes in human colorectal and gastric cancers
Department of Gastroenterology, St Radboud University Hospital, Nijmegen, The Netherlands and
1 Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra, Australia
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
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
isoenzymes in these tissues are available. The aim of this study was to determine the protein levels of the two
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,
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
class isoenzyme levels after malignant transformation. Gastric tumors had significantly lower expression of both
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.
Abbreviations: GST, glutathione S-transferase
2 To whom correspondence should be addressed Email: w.peters{at}gastro.azn.nl
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