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/EBPdelta 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.
Mesh Terms:
Acetylation, Animals, Base Sequence, Cell Line, Tumor, Cyclic AMP Response Element-Binding Protein, Cyclooxygenase 2, DNA-Binding Proteins, Dinoprostone, Gene Expression Regulation, Neoplastic, Genes, Reporter, Histones, Humans, Lysophospholipids, Mice, Molecular Sequence Data, NIH 3T3 Cells, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Sphingosine, Transcription Factors, Transcription, Genetic, Two-Hybrid System Techniques
Mol. Cell. Endocrinol.
Date: Feb. 13, 2008
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