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 characteri stically restricted to tumours expressing oestrogen receptors (ER). We now describe oestrogen-stimulated growth of the ER-negative human bre ast cancer cell line MDA-MB-231, subclone 10A. Cell culture experiment s confirmed that 10A cells are unresponsive to a wide concentration ra nge of oestradiol (E(2)) in vitro. Analysis of growth curves in vivo r evealed significantly longer tumour volume doubling times for the cont rol group than for the E(2)-treated group. Cell cycle studies using in vivo labelling with bromodeoxyuridine (BrdU) and flow cytometric anal ysis showed essentially equal potential doubling times for controls an d E(2)-treated animals. These results suggest that E(2) reduces cell l oss, rather than stimulating proliferation. E(2)-stimulated growth was seen in both natural killer (NK) cell producing athymic (nude) mice a nd congenitally NK cell deficient beige nude mice, We conclude that E( 2)-induced natural killer cell suppression is an unlikely mechanism of action.