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

作者：Dong Chunmin; Yuan Lin; Dai Jun; Lai Ling; Mao Lulu; Xiang Shulin; Rowan Brian; Hill Steven M^*

来源：Steroids, 2010, 75(12): 944-951.

DOI：10.1016/j.steroids.2010.06.002

• ROR alpha
• ER alpha
• Breast cancer
• Melatonin
• Cell proliferation

Luciferase reporter constructs and transient co-transfection approaches demonstrate that elevated expression of ROR alpha 1 augments 17-beta-estradiol (E(2))-induced transcriptional activation of the full-length ER alpha, but not truncated ER alpha 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 ERa by ROR alpha 1 and E(2). Gel mobility shift and co-immunoprecipitation (IP)/pull-down assays demonstrate that ROR alpha 1 and ER alpha do not interact directly at the DNA-binding level or as heterodimers, however, ROR alpha 1 augments E(2)-induced pS2 and cyclin D1 mRNA expression while MLT inhibits ROR alpha 1/E(2)-induced expression of pS2 and cyclin D1 in MCF-7 cells.

• 出版日期2010-12