Sphingosine-1-phosphate regulates the expression of the liver receptor homologue-1

In this study, we examined the role of sphingosine-1-phosphate (S1P) in regulating the transcription of the liver receptor homologue-1 (LRH-1) in breast cancer cells. We show that S1P induces LRH-1 mRNA expression in MCF-7 cells in a prostaglandin E2 (PGE2)-dependent manner. Both S1P and PGE2 stimulate the recruitment of LRH-1, cAMP response element binding protein (CREB), CCAAT/enhancer binding proteins (C/EBP), and RNA Polymerase II (Pol II) to the LRH-1 promoter, as well as increase acetylation of histone H3 in this region of chromatin. S1P and PGE2 promote the direct interaction of CREB and LRH-1, which is potentiated by C/EBPδ and the coactivators CREB-binding protein (CBP), and steroid receptor coactivator-3 (SRC-3). CREB and LRH-1 synergistically increase LRH-1 transcription, suggesting an integral role for LRH-1 in regulating the transcription of its own gene.