Activation of Estrogen Receptor-Beta-Dependent Transcription by Estrogen-Independent Pathways
Abstract
There are two known receptors for estrogens, ER alpha and ER beta. The existence of ER beta was only recently appreciated, and little is understood about its ability to be activated by intracellular signaling pathways in the absence of estrogens. The purpose of this research program is to characterize the ability of ER beta to by activated by various ligand-independent signaling pathways, and to characterize the structural regions of ER beta, in comparison to ER alpha, that regulate how this receptor subtype responds to intracellular cross-talk. We have found that stimulation of HeLa cells with forskolin and IBMX results in the activation of ER alpha and ER beta dependent expression in a receptor-dependent and promoter context- dependent manner, and that protein kinase A mediates this response. Factors that interact with an AP-1 binding site contribute to forskolin/IBMX activation of estrogen receptor<dependent gene expression, and do so in a manner that does not require the A/B domain of either receptor. At least c-Jun is able to stimulate ER alpha activity via the AP-1 binding site. Multiple coactivator proteins, predominantly of the steroid receptor coactivator (SRC) family and CREB binding protein (CBP) can stimulate ER alpha and ER beta activity induced by forskolin)IBMX pathways indicating that these coactivators can functionally interact with these receptors in the absence of ligand.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA400004
Entities
People
- Carolyn L. Smith
Organizations
- Baylor College of Medicine