title: MCF7/LCC2: a 4-hydroxytamoxifen resistant human breast cancer variant that retains sensitivity to the steroidal antiestrogen ICI 182,780.
abstract: 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.
authors.affiliation: Vincent Lombardi Cancer Center, Georgetown University Medical School, Washington, D.C. 20007.
authors.forename: N
authors.initials: N
authors.lastname: Brünner
authors.forename: T L
authors.initials: TL
authors.lastname: Frandsen
authors.forename: C
authors.initials: C
authors.lastname: Holst-Hansen
authors.forename: M
authors.initials: M
authors.lastname: Bei
authors.forename: E W
authors.initials: EW
authors.lastname: Thompson
authors.forename: A E
authors.initials: AE
authors.lastname: Wakeling
authors.forename: M E
authors.initials: ME
authors.lastname: Lippman
authors.forename: R
authors.initials: R
authors.lastname: Clarke
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol