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Glutathione Transferase Activity and Isoenzyme Composition in Primary Human Breast Cancers¹

Department of Medicine, University of California at San Diego, San Diego, California [T. C. S.]; Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland, Oregon 97201 [G. C., K. E. C., B. J. S. S., E. J. K., W. D. H.]; Department of Pathology, St. Elizabeth's Hospital, Boston, Massachusetts 02135 [N. A. B.] and Department of Biochemistry, University of Uppsala, Uppsala, Sweden [B. M.]

The human glutathione transferase (GSTs) are a multigene family of detoxication enzymes with patterns of expression that are both tissue specific and genetically determined. Changes in the levels of one or more GST isoenzymes have been associated with the development of anticancer drug resistance in cultured cell lines. In this study, total GST activity and GST isoenzyme composition have been determined for 45 primary human breast carcinomas using a 1-chloro-2,4-dinitrobenzene substrate assay and Western blotting, respectively. The GST activity ranged from 5–208 mU/mg protein with a mean of 67 mU/mg protein (±44 SD). GST- isoenzyme protein was detectable on Western blots in 44 of 45 samples. Mu Class GST protein was detected in 18 of 38 samples and undetectable in 20 of the 38 samples tested. By polymerase chain reaction analysis of genomic DNA, the absence of mu class GST in breast tumors was determined to be due to the deletion of the gene for GST- in the DNA of those tumors. None of the 43 primary human breast cancer samples tested contained detectable alpha class GST protein. Neither the total GST activity of tumor samples, the quantity of GST- protein, nor the presence or absence of mu class GST correlated with other factors known to be of prognostic significance including tumor size, nodal status, estrogen receptor protein positivity, or progesterone receptor protein positivity. Substantial differences exist among primary breast carcinomas in both the amount of GST activity and GST isoenzyme composition. However, these are not tightly linked either to tumor stage or to hormone receptor status. Whether the levels of these enzymes are independent predictors of either risk of recurrence or response to anticancer therapy has yet to be tested directly.

¹ A preliminary report of this work appeared in abstract form in Proc. Am. Assoc. Cancer Res., 29: 1208, 1988. Supported by grants from Bristol-Myers Squibb Co. and the Swedish Cancer Society.

² T. C. S. is a recipient of a Faculty Development Award in Clinical Pharmacology from the Pharmaceutical Manufacturers Association Foundation, Washington, DC 20005.

³ To whom requests for reprints should be addressed, at Division of Hematology and Medical Oncology, Oregon Health Sciences University L586, 3181 SW Sam Jackson Park Road, Portland, OR 97201.

Received 3/19/90. Accepted 7/30/90.

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