Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells.

Abstract

While many physiological effects of estrogens (E) are due to regulation of gene transcription by liganded estrogen receptors (ERs), several effects are also mediated, at least in part, by rapid non-genomic actions of E. Though the relative importance of rapid versus genomic effects in the central nervous system is controversial, we showed previously that membrane-limited effects of E, initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could potentiate transcriptional effects of 17β-estradiol from an estrogen response element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors and activators in a pharmacological approach, we show that activation of phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways, dependent on a Gαq coupled receptor signaling are important in this transcriptional potentiation. We further demonstrate, using ERα phospho-deficient mutants, that E2-BSA mediated phosphorylation of ERα is one mechanism to potentiate transcription from an ERE reporter construct. This study provides a possible mechanism by which signaling from the membrane is coupled to transcription in the nucleus, providing an integrated view of hormone signaling in the brain.

• Authors: Sara Clark, Jennifer Rainville, Xing Zhao, Benita S Katzenellenbogen, Donald Pfaff, Nandini Vasudevan
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 139 Pg. 45-53 (Jan 2014) ISSN: 1879-1220 [Electronic] England
• PMID: 24121066 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Androstadienes
• Butadienes
• ESR1 protein, human
• Estrogen Receptor alpha
• Nitriles
• Phosphoinositide-3 Kinase Inhibitors
• U 0126
• estradiol-bovine serum albumin
• Serum Albumin, Bovine
• Estradiol
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Butadienes (pharmacology)
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Enzyme Activation
• Estradiol (pharmacology, physiology)
• Estrogen Receptor alpha (genetics, metabolism)
• HEK293 Cells
• Humans
• MAP Kinase Signaling System
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Neuroblastoma
• Nitriles (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Protein Processing, Post-Translational
• Proto-Oncogene Proteins c-akt (metabolism)
• Response Elements
• Serum Albumin, Bovine (pharmacology, physiology)
• Transcription, Genetic
• Transcriptional Activation
• Wortmannin