ESTRADIOL STIMULATES GROWTH OF ESTROGEN RECEPTOR-NEGATIVE MDA-MB-231 BREAST-CANCER CELLS IN IMMUNODEFICIENT MICE BY REDUCING CELL LOSS

Growth stimulation by oestrogens in immunodeficient mice is characteristically restricted to tumours expressing oestrogen receptors (ER). We now describe oestrogen-stimulated growth of the ER-negative human breast cancer cell line MDA-MB-231, subclone 10A. Cell culture experiments confirmed that 10A cells are unresponsive to a wide concentration range of oestradiol (E(2)) in vitro. Analysis of growth curves in vivo revealed significantly longer tumour volume doubling times for the control group than for the E(2)-treated group. Cell cycle studies using in vivo labelling with bromodeoxyuridine (BrdU) and flow cytometric analysis showed essentially equal potential doubling times for controls and E(2)-treated animals. These results suggest that E(2) reduces cell loss, rather than stimulating proliferation. E(2)-stimulated growth was seen in both natural killer (NK) cell producing athymic (nude) mice and congenitally NK cell deficient beige nude mice, We conclude that E(2)-induced natural killer cell suppression is an unlikely mechanism of action.