title: Melatonin inhibits mitogenic cross-talk between retinoic acid-related orphan receptor alpha (RORalpha) and ERalpha in MCF-7 human breast cancer cells.
abstract: Luciferase reporter constructs and transient co-transfection approaches demonstrate that elevated expression of RORalpha1 augments 17-beta-estradiol (E(2))-induced transcriptional activation of the full-length ERalpha, but not truncated ERalpha constructs (ABCD or CDEF), in MCF-7 breast cancer and HEK293 embryonic kidney cells, and that physiologic concentrations of MLT inhibit the individual and combined transcriptional activity of ERalpha by RORalpha1 and E(2). Gel mobility shift and co-immunoprecipitation (IP)/pull-down assays demonstrate that RORalpha1 and ERalpha do not interact directly at the DNA-binding level or as heterodimers, however, RORalpha1 augments E(2)-induced pS2 and cyclin D1 mRNA expression while MLT inhibits RORalpha1/E(2)-induced expression of pS2 and cyclin D1 in MCF-7 cells.
authors.affiliation: Department of Structural and Cellular Biology, Tulane Cancer Center and Tulane University Health Sciences Center, 1430 Tulane Ave., SL-49, New Orleans, LA 70112, USA.
authors.forename: Chunmin
authors.initials: C
authors.lastname: Dong
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
authors.forename: Ling
authors.initials: L
authors.lastname: Lai
authors.forename: Lulu
authors.initials: L
authors.lastname: Mao
authors.forename: Shulin
authors.initials: S
authors.lastname: Xiang
authors.forename: Brian
authors.initials: B
authors.lastname: Rowan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hill
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D020239:Receptor Cross-Talk / Q000187:drug effects*; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D004958:Estradiol; D008550:Melatonin