title: The effect of the new SERM arzoxifene on growth and gene expression in MCF-7 breast cancer cells.
abstract: The benzothiophene arzoxifene is a new 3rd generation selective estrogen receptor (ER) modulator (SERM). We have investigated the effect of arzoxifene on growth and gene expression in the estrogen receptor alpha (ERalpha) positive human breast cancer cell line MCF-7. Arzoxifene inhibits cell growth as effectively as the antiestrogen tamoxifen. Northern analysis revealed that arzoxifene exerts a statistically significant inhibition of pS2 and progesterone receptor B mRNA expression. Significant agonistic effect was observed on the antitrypsin mRNA expression. In contrast to estradiol and tamoxifen, arzoxifene does not upregulate cathepsin D mRNA and protein expression. The metabolite of arzoxifene (ARZm) is a more potent growth inhibitor of MCF-7 cells than arzoxifene. A tamoxifen resistant MCF-7 subline displayed a significant dose-dependent growth inhibition to ARZm, whereas an ICI 182,780 resistant cell line only responded to high concentration. Our results indicate that arzoxifene and especially ARZm are efficient growth inhibitors of ER positive human breast cancer cells, including tamoxifen resistant cells. Moreover, arzoxifene displays less estrogen agonistic effects in MCF-7 cells than tamoxifen.
authors.affiliation: Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Cecilie T
authors.initials: CT
authors.lastname: Freddie
authors.forename: Søren S
authors.initials: SS
authors.lastname: Larsen
authors.forename: Monica
authors.initials: M
authors.lastname: Bartholomaeussen
authors.forename: Anne E
authors.initials: AE
authors.lastname: Lykkesfeldt
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002402:Cathepsin D / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D010880:Piperidines; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; C115121:LY 353381; D002402:Cathepsin D