EXPRESSION OF SELENIUM-DEPENDENT GLUTATHIONE-PEROXIDASE IN HUMAN BREAST-TUMOR CELL-LINES

In estrogen receptor (ER)-positive breast cancer cell lines, very low expression of glutathione peroxidase-1 (GPX-1) activity and hgpx1 mRNA has been observed. Such cell lines have been used as models in studie s of resistance to redox cycling anticancer drugs. In particular, larg e increases in GPX-1 activity levels by expression of transfected GPX- 1 cDNA have been shown to confer some resistance to such drugs. It has never been determined that such low GPX-1 expression is a common feat ure of breast cancer. Based on previous limited surveys of breast canc er cell lines, it has been suggested that there may be an inverse corr elation between ER status and GPX-1 production. Here wt! report the re sults from a larger survey of breast cancer cell lines, including six recently isolated cell lines. A near absence of hgpx1 mRNA expression was observed in 3 of 13 ER-negative cell lines; 1 of 4 ER-positive cel l lines had high production of GPX-1. Both observations weaken the pro posed inverse correlation between ER status and GPX-1 production. We h ave evidence to suggest that one cell line, COH-BR-5 (ER-negative), la cked hgpx1 gene expression prior to culture. This is based on the find ing of stable hgpx1 gene expression during serial culture of ER-negati ve breast cancer cell lines newly isolated from malignant effusion and absence of hgpx1 mRNA expression in COH-BR-5. Expression of hgpx2 mRN A (producing GPXGI, the GI tract GPX) was detected in several long and newly established, ER-negative breast cancer cell lines. Cell lines, COH-BR-5 and MDA-MB-175, expressed only hgpx2 mRNA. The hgpx2 mRNA was detected in COH-BR-5 and COH-BR-7 at low passage number, suggesting t hat hgpx2 2 gene expression occurs in breast cancer malignant effusion . Thus, studies of the role of GPX in redox drug resistance may accoun t for changes in hgpx2 gene expression. Phospholipid hydroperoxide GPX activity was not found to be generally elevated above normal tissue l evels in newly established breast cancer-derived cell lines.