Melatonin inhibits mitogenic cross-talk between retinoic acid-related orphan receptor alpha (RORalpha) and ERalpha in MCF-7 human breast cancer cells.
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.
Dong
Chunmin
C
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.
Yuan
Lin
L
Dai
Jun
J
Lai
Ling
L
Mao
Lulu
L
Xiang
Shulin
S
Rowan
Brian
B
Hill
Steven M
SM
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
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