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.