title: Differential effects of raloxifene, tamoxifen and fulvestrant on a murine mammary carcinoma.
abstract: The purpose of this study was to evaluate the effect of the selective estrogen receptor modulators raloxifene and tamoxifen and of the pure antiestrogen fulvestrant on tumor growth and progesterone receptor (PR) expression in an experimental model of breast cancer. The effects of these compounds on cell proliferation were studied in primary cultures of a progestin-dependent mammary carcinoma tumor line, in the presence of medroxyprogesterone acetate (MPA) or 17-beta-estradiol (E2). In in vivo studies the tumor was inoculated subcutaneously in BALB/c female mice treated with 20 mg MPA depot. Raloxifene (12.5 mg/kg) or tamoxifen (5 mg/kg) were administered in daily doses or E2 silastic pellets (5 mg) were implanted. When the tumors reached about 25-50 mm2 MPA was removed in half of the animals. E2 induced complete tumor regressions, tamoxifen inhibited tumor growth in vivo while raloxifene disclosed proliferative effects in animals in which MPA had been removed. In vitro, E2 inhibited cell proliferation at concentrations higher than 10(-14)M. Raloxifene and fulvestrant, but not tamoxifen, partially reverted E2-induced inhibition. Fulvestrant and tamoxifen inhibited MPA-induced cell proliferation while raloxifene had a stimulatory effect. Tamoxifen and E2 increased, raloxifene induced no effect, and fulvestrant significantly decreased PR expression. In this study we provide evidence for differential effects of tamoxifen and raloxifene on experimental mammary tumors. Since raloxifene is under evaluation for use in breast cancer prevention, these results may have important clinical implications.
authors.affiliation: Instituto de Biología y Medicina Experimental (Consejo Nacional de Investigaciones Científicas y Técnicas--CONICET), Buenos Aires, Argentina.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Lamb
authors.forename: Luisa A
authors.initials: LA
authors.lastname: Helguero
authors.forename: Victoria
authors.initials: V
authors.lastname: Fabris
authors.forename: Colombo
authors.initials: C
authors.lastname: Lucas
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanari
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008555:Melitten / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018997:Chorionic Gonadotropin, beta Subunit, Human; D020847:Estrogen Receptor Modulators; D011980:Receptors, Progesterone; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D013629:Tamoxifen; D008555:Melitten; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D017258:Medroxyprogesterone Acetate