Melatonin inhibits mitogenic cross-talk between retinoic acid-related orphan receptor alpha (RORα) and ERα in MCF-7 human breast cancer cells

Luciferase reporter constructs and transient co-transfection approaches demonstrate that elevated expression of RORα1 augments 17-β-estradiol (E2)-induced transcriptional activation of the full-length ERα, but not truncated ERα 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 ERα by RORα1 and E2. Gel mobility shift and co-immunoprecipitation (IP)/pull-down assays demonstrate that RORα1 and ERα do not interact directly at the DNA-binding level or as heterodimers, however, RORα1 augments E2-induced pS2 and cyclin D1 mRNA expression while MLT inhibits RORα1/E2-induced expression of pS2 and cyclin D1 in MCF-7 cells.