Oestradiol stimulates growth of oestrogen 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 (E₂) in vitro. Analysis of growth curves in vivo revealed significantly longer tumour volume doubling times for the control group than for the E₂-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 E₂-treated animals. These results suggest that E₂ reduces cell loss, rather than stimulating proliferation. E₂-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 E₂-induced natural killer cell suppression is an unlikely mechanism of action.