Abstract
An increasing body of evidence indicates that glutathione S-transferases play a role in the intrinsic and acquired resistance of tumours to anticancer drugs. In view of the wide use of tumour cell lines to understand the factors which confer either sensitivity or resistance to chemotherapeutic agents we have determined glutathione S-transferase (GST) activity and isozyme composition in nine human cell lines. These data have been compared with the values obtained in solid tumours. In most cases overall GST activity was higher in the tumours than in the cell lines. This was most pronounced for the breast tumour samples relative to MCF7 cell line. The pi class GST subunit was present at similar concentration in the cell lines and the tumours, and in most cases was the most abundant subunit present. The alpha and mu class GST were expressed in most of the cell lines but at much lower concentration than the pi class subunit. Also considerable variability particularly in the expression of the mu subunits was observed. This was also the case for the expression of these subunits in the solid tumour samples. The levels of these GSTs (when expressed) in the solid tumours was invariably higher than that observed in the cell lines. There are therefore several similarities but also some significant differences in GST expression in solid tumours and cell lines. Whether the differences are because expression is lost during the generation of the cell lines or whether it reflects the individuality of human tumours remains to be clearly established.
Highlights
In view of the general use of cell lines as models for solid tumours and for the study of drug resistance glutathione S-transferase (GST) activity and isoenzyme profiles from a series of nine human tumour cell lines have been established and compared to the GST profiles detected in solid tumours from the same tissue type
Significant variation in activity between the lines was observed. This was the case for the breast cancer cell line, MCF7 which had by far the lowest activity (3.5 nmol conjugate formed min-I mg protein-') and was approximately 60-fold lower than the ovarian adenocarcinoma cell line PEO4 (210.3 nmol CDNB conjugated min- mg protein-1)
This difference in GST activity was reflected in the glutathione S-transferase isoenzyme content
Summary
The following cell lines: human breast carcinoma MCF7; ovarian adenocarcinoma PEO4; bladder carcinoma EJ; lung carcinoma NCI-H322 and NCI-H358; colonic carcinoma HT29; and lung fibroblast EF484, were grown in RP-I 1640. The LS174T, a human colonic carcinoma line, was grown in MEM containing non-essential amino acids. The human hepatoma line, HepG2, was grown in DMEM medium and the mouse hepatoma line Hepa I in Ham's F12. C = cell line; T = solid tumour; N = normal tissue. The cell lines taken were MCF7, HT29, NCI H322, PEO4, EJ and. HepG2 for breast, colon, lung, ovary, bladder and liver respectively. More than one tumour is shown in certain cases to demonstrate the extremes observed in GST expression. The standards (STD) were isolated from human liver and lung (Hayes et al, 1983; Stockman et al, 1987)
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