A BREAST-CANCER CLONE SELECTED BY TAMOXIFEN HAS INCREASED GROWTH-RATEAND REDUCED SENSITIVITY TO DOXORUBICIN

The in vivo growth rate and the chemosensitivity patterns of a cell cl one selected by tamoxifen from the estrogen receptor-negative human br east cancer cell line MDA-MB-231 was studied in the nude mouse model a nd with flow cytometry. To investigate the growth rate of the wild-typ e and clone cells in vivo, the cells were inoculated into the opposite flanks of 5 male nude mice. Drug sensitivity to doxorubicin (10 ng/mL ), vinblastine (1 ng/mL), and paclitaxel (1 ng/mL) was examined in wil d-type/clone cell mixture using flow cytometry. Northern blot techniqu e was used to study the expression of mdr-1 messenger RNA in both the wild-type and the clone cells. The tumors derived from the clone and w ild-type cells were, following a 3-week growth period, 260.2 +/- 78.8 mm2 vs. 68.3 +/- 50.8 mm2 in size, respectively (P < 0.001). Following a 28-day continuous exposure, doxorubicin was selectively toxic to th e wild-type cells, while having no apparent effect on the clone popula tion. However, paclitaxel- and vinblastine-treated wild-type/clone cel l mixtures did not exhibit a differential cytotoxic effect on either c ell population. It was concluded that the clone selected by tamoxifen shows an aggressive growth rate in vivo and an altered chemosensitivit y pattern to doxorubicin in vitro.