Modulation by oestrogen and progestins/antiprogestins of alpha interferon receptor expression in human breast cancer cells

Abstract

Human breast cancer ZR-75-1 cells expressed 1516 (105) (mean [S.D.]) interferon (IFN) receptors (IFNR) per cell with K d of 0.61 (0.15) nmol/l. Oestrogen independent ZR-PR-LT and tamoxifen resistant ZR-75-9a1 8 μmol/l cells expressed similar numbers of IFNR. ZR-75-9a1 cells, which had been maintained in the absence of tamoxifen or known oestrogenic activity for 46 weeks, expressed a significantly higher number of IFNR (3170 [315]). Exposure of ZR-75-1 cells to 10 −9 mol/l 17β-oestradiol (E2) led to a consistent reduction in IFNR numbers whilst 10 −6 mol/l tamoxifen slightly increased IFNR expression. Since IFN increases oestrogen receptors in this cell line, IFN and E2 appear to have opposite effects on expression of each others' receptor. 10 −9 mol/l medroxy progesterone acetate and mifepristone significantly increased IFNR numbers whilst ORG 2058 decreased IFNR expression and ZK 98.299 had no effect. Progestin/antiprogestin induced IFNR increase in this cell line correlated with down-regulation of progesterone receptor (PR). Thus an IFN/ER/PR axis may exist in ZR-75-1 cells and variants.