SIP1/NHERF2 enhances estrogen receptor alpha transactivation in breast cancer cells

Abstract

The estrogen receptor alpha (ERα) is a ligand-activated transcription factor that possesses two activating domains designated AF-1 and AF-2 that mediate its transcriptional activity. The role of AF-2 is to recruit coregulator protein complexes capable of modifying chromatin condensation status. In contrast, the mechanism responsible for the ligand-independent AF-1 activity and for its synergistic functional interaction with AF-2 is unclear. In this study, we have identified the protein Na+/H+ Exchanger RegulatoryFactor 2 (NHERF2) as an ERα-associated coactivator that interacts predominantly with the AF-1 domain of the nuclear receptor. Overexpression of NHERF2 in breast cancer MCF7 cells produced an increase in ERα transactivation. Interestingly, the presence of SRC-1 in NHERF2 stably overexpressing MCF7 cells produced a synergistic increase in ERα activity. We show further that NHERF2 interacts with ERα and SRC-1 in the promoter region of ERα target genes. The binding of NHERF2 to ERα in MCF7 cells increased cell proliferation and the ability of MCF7 cells to form tumors in a mouse model. We analyzed the expression of NHERF2 in breast cancer tumors finding a 2- to 17-fold increase in its mRNA levels in 50% of the tumor samples compared to normal breast tissue. These results indicate that NHERF2 is a coactivator of ERα that may participate in the development of estrogen-dependent breast cancer tumors.

Nuclear tristetraprolin acts as a corepressor of multiple steroid nuclear receptors in breast cancer cells

“…ERα transactivation activity was determined using a luciferase reporter gene driven by a promoter containing three estrogen responsive elements (ERE-Tk-LUC) that has been previously described [4] , [26] . To test the transactivation activity of PR, AR.…”

Electrospun polyurethane-dextran nanofiber mats loaded with Estradiol for post-menopausal wound dressing

“…The fibroblasts must bind to the Estradiol loaded PU-dextran nanofibers scaffold, so the quality of extracellular matrix is also crucial for re-epithelialization, which is satisfied by the morphology of nanofiber matrix. Moreover the hormone estrogen (␤-estradiol) has a key role in cell proliferation and differentiation [30] and hence the cell growth is more in Estradiol loaded PU nanofibers compared to pristine PU. But the Estradiol loaded PU-dextran nanofibers showed much enhanced cell growth due to the combined effect of dextran and estradiol.…”

Estradiol induces HOTAIR levels via GPER-mediated miR-148a inhibition in breast cancer

“…The hormone estrogen (17β-estradiol, E2) has a key role in cell prolife[ration and differentiation through receptor binding and activation [ 15 - 17 ]. The effects of E2 have been widely analyzed in the human mammary gland, where it is responsible for normal epithelial growth and for the development of 70–80% of human breast cancer tumors [ 18 ]. Approximately 70% of human breast cancer is estrogen receptor-α positive (ER+) and up to 20% of breast cancer is triple-negative breast cancer (TNBC) [ 19 ].…”