A breast cancer clone selected by tamoxifen has increased growth rate and reduced sensitivity to doxorubicin.
The in vivo growth rate and the chemosensitivity patterns of a cell clone selected by tamoxifen from the estrogen receptor-negative human breast cancer cell line MDA-MB-231 was studied in the nude mouse model and with flow cytometry. To investigate the growth rate of the wild-type 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 wild-type/clone cell mixture using flow cytometry. Northern blot technique 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 wild-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 the wild-type cells, while having no apparent effect on the clone population. However, paclitaxel- and vinblastine-treated wild-type/clone cell mixtures did not exhibit a differential cytotoxic effect on either cell population. It was concluded that the clone selected by tamoxifen shows an aggressive growth rate in vivo and an altered chemosensitivity pattern to doxorubicin in vitro.
Maenpaa
J U
JU
Department of Medicine/Oncology, UTHSCSA, San Antonio, TX 78284-7884.
Wurz
G T
GT
Baker
W J
WJ
Wiebe
V J
VJ
Emshoff
V D
VD
Koester
S K
SK
Seymour
R C
RC
Koehler
R E
RE
DeGregorio
M W
MW
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; D004317:Doxorubicin