Reduced tamoxifen accumulation is not associated with stimulated growth in tamoxifen resistance.
To study tamoxifen resistance-stimulated growth, 30 female ovariectomized nude mice were implanted with tamoxifen-resistant tumors and treated with 10-1000 micrograms/day of tamoxifen citrate subcutaneously. Tamoxifen stimulated MCF-7 tumor growth in a dose-dependent manner, with tumoral tamoxifen concentrations increasing proportionally to the dose (1-13 nmol/g), as measured by high-performance liquid chromatography (HPLC). Flow-cytometric analysis revealed that tamoxifen-resistant tumors had a different DNA content as compared with wild-type MCF-7 cells. In contrast to earlier results, these data suggest that tamoxifen resistance-stimulated growth is associated with increasing rather than decreasing tumoral tamoxifen concentrations. Furthermore, the observed ploidy changes in the tamoxifen-resistant tumors imply that a genetic basis may exist for the development of tamoxifen resistance.
Maenpaa
J
J
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884.
Wiebe
V
V
Wurz
G
G
Koester
S
S
Emshoff
V
V
Seymour
R
R
DeGregorio
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy; D013629:Tamoxifen / Q000737:chemistry / Q000627:therapeutic use*
D004273:DNA, Neoplasm; D013629:Tamoxifen