MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780.
The development of resistance to the antiestrogen tamoxifen occurs in a high percentage of initially responsive patients. We have developed a new model in which to investigate acquired resistance to triphenylethylenes. A stepwise in vitro selection of the hormone-independent human breast cancer variant MCF-7/LCC1 against 4-hydroxytamoxifen produced a stable resistant population designated MCF7/LCC2. MCF7/LCC2 cells retain levels of estrogen receptor expression comparable to the parental MCF7/LCC1 and MCF-7 cells. Progesterone receptor expression remains estrogen inducible in MCF7/LCC2 cells, although to levels significantly lower than observed in MCF-7 and MCF7/LCC1 cells. MCF7/LCC2 cells form tumors in ovariectomized nude mice without estrogen supplementation, and these tumors are tamoxifen resistant but can be estrogen stimulated. Significantly, MCF7/LCC2 cells have retained sensitivity to the steroidal antiestrogen ICI 182,780. These data suggest that some breast cancer patients who acquire resistance to tamoxifen may not develop cross-resistance to treatment with steroidal antiestrogens.
Brünner
N
N
Vincent Lombardi Cancer Center, Georgetown University Medical School, Washington, D.C. 20007.
Frandsen
T L
TL
Holst-Hansen
C
C
Bei
M
M
Thompson
E W
EW
Wakeling
A E
AE
Lippman
M E
ME
Clarke
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol