© 1990 Oxford University Press
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Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue
Imperial Cancer Research Fund, Molecular Pharmacology Group and Drug Metabolism Hugh Robson Building, George Square, Edinburgh EH8 9XD
1Department of Clinical Chemistry, Royal Infirmary of Edinburgh Lauriston Place, Edinburgh
2Imperial Cancer Research Fund, Clinical Oncology Unit, Guy's Hospital St Thomas Street, London
3Department of Radiology, ICRF Clinical Oncology Unit. Churchill Hospital Oxford, UK
4Department of Pharmacology and Oncology, Mayo Clinie Rochester MN 55905, USA
5To whom correspondence should be addressed
The level of expression of glutathione S-transferases (GSTs) and cytochrome P450s in breast tissue are potentially important determinants in both the susceptibility of this tissue to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. In this study we have investigated the expression of these proteins in 41 tumor and surrounding normal breast tissue samples by measurement of substrate metabolism, Western blot analysis and immunohistochemistry. In addition, we have quantitated the concentration of alpha, mu and pi class GST subunits using radioimmunoassay. All three classes of GST were expressed in breast tissue. The p1 and mu class enzymes preponderate. Both the polymorphic mu class GST as well as a further form, present in all Individuals, were found in high concentration. The polymorphic mu class GST was expressed in 
50% of the samples, which is consistent with the frequency of this polymorphism in the population and therefore does not appear to be a factor in susceptibility to this disease. Interestingly, although levels of the alpha class GST were very low, in two tumor samples extremely high levels of the B1B1 subunit were detected. Immunohisto chemical studies showed significant variability in the localization of the pi class of GST between normal epithelial cells, infiltrating plasma cells and tumor cells, and in some samples GST pi appeared to be almost absent from the tumor tissue. No direct, or inverse correlation was found between GST pi concentration determined by radioimmunoassay and estrogen receptor levels. However, when studied by immuno histochemistry estrogen receptor negative tumors did tend to have higher GST pi content. The only cytochrome P450 detectable by Western blot analysis was a member of the P450IIC gene family. This was apparently distinct from the P4S0IIC proteins expressed in the liver and was detected in normal and tumor tissues to a similar extent.
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