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.
Hadizadeh
Shervin
S
School of Biology, Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, United States.
King
Denine N
DN
Shah
Shaili
S
Sewer
Marion B
MB
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D020798:Two-Hybrid System Techniques
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006657:Histones; D008246:Lysophospholipids; C082631:NR5A2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C060506:sphingosine 1-phosphate; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013110:Sphingosine