title: The Wnt/β-catenin signaling pathway is involved in the antitumor effect of fulvestrant on rat prolactinoma MMQ cells.
abstract: Although an antiestrogen treatment for estrogen-dependent diseases, such as breast cancers, has been reported, the effect of this endocrine therapy on prolactinomas and its possible mechanism are unclear. This study investigates the antitumor effect of fulvestrant, which is a new estrogen receptor antagonist, on rat prolactinoma MMQ cells and the possible roles of the Wnt/β-catenin signaling pathway that is involved in this antitumor effect. To investigate the antitumor effect of fulvestrant, the effects of exposure to gradient doses of fulvestrant (0, 0.04, 1, 25, and 625 nM) on the proliferation of cells and the secretion of prolactin (PRL) were studied. Then, the expression levels of the Wnt/β-catenin signaling pathway-related proteins β-catenin and Wnt inhibitory factor-1 (WIF-1) were measured to investigate their possible roles in the antitumor effect of fulvestrant. The cells were also treated with decitabine (10 μM) to investigate the epigenetic mechanism of WIF-1 expression. The proliferation of MMQ cells and the secretion of PRL were suppressed by fulvestrant in a dose-dependent manner (up to 57.0 ± 3.9 % and 51.2 ± 4.9 %, respectively). β-Catenin expression was downregulated and was positively correlated with ER-α expression (P<0.01). As a tumor suppressor, WIF-1 expression was upregulated and was negatively correlated with ER-α expression (P<0.01). Furthermore, WIF-1 expression was upregulated via the hypomethylation of the promoter by decitabine, and cellular proliferation was correspondingly suppressed (37.8 ± 4.3 %). Antitumor effect of fulvestrant was partially disrupted by SB 216763 via activation of the Wnt/β-catenin pathway. In conclusion, through the Wnt/β-catenin signaling pathway, fulvestrant can suppress the proliferation of MMQ cells and the secretion of PRL.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, 6 Tiantan Xili, Beijing, 100050, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Songbai
authors.initials: S
authors.lastname: Gui
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D000077267:Fulvestrant; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015175:Prolactinoma / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C495268:Ctnnb1 protein, rat; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; C521045:Wif1 protein, rat; D051176:beta Catenin; D000077267:Fulvestrant; D004958:Estradiol; D000077209:Decitabine; D001374:Azacitidine