title: Arsenic trioxide (As2O3) inhibits expression of estrogen receptor-alpha through regulation of the mitogen-activated protein kinase (MAPK) pathway in endometrial cancer cells.
abstract: Given that prolonged exposure to unopposed estrogen has been implicated in endometrial carcinogenesis, our goal was to evaluate the effect of As(2)O(3) on regulation of estrogen receptor-alpha (ERa) expression in endometrial cancer cells. As(2)O(3) inhibited ER- mRNA and protein expression in a dose-dependent manner in both the Ishikawa and ECC-1 endometrial cancer cell lines. Treatment with As(2)O(3) resulted in rapid phosphorylation of the p42/p44 MAPK which could be abolished by addition of the MAPK inhibitor, U0126. Although treatment with U0126 alone resulted in up-regulation of ER- mRNA and protein, exposure to U0126 in combination with As(2)O(3) counteracted As(2)O(3)'s inhibitory effect on ER- expression. We provide evidence that As(2)O(3) inhibits ER- mRNA and protein expression in endometrial cancer cells, potentially through interaction with the MAPK pathway. Thus, As(2)O(3) may be valuable for its anti-estrogenic activity in combination with its anti-tumorigenic effects and be a novel therapeutic agent for endometrial cancer.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. vbae@unch.unc.edu
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.forename: John F
authors.initials: JF
authors.lastname: Boggess
authors.forename: Paola A
authors.initials: PA
authors.lastname: Gehrig
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001152:Arsenicals; D047628:Estrogen Receptor alpha; D010087:Oxides; D020928:Mitogen-Activated Protein Kinases; D000077237:Arsenic Trioxide