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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
BMPR2 expression is suppressed by signaling through the estrogen receptor
Eric D Austin1, Rizwan Hamid, Anna R Hemnes
1Department of Pediatrics, Vanderbilt University Medical Center, 1161 21st Ave S Suite DD-2205, Nashville, TN 37232-2578, USA. eric.austin@vanderbilt.edu.
Biology of Sex Differences
|February 22, 2012
Summary
Estrogen signaling directly suppresses bone morphogenetic protein receptor type 2 (BMPR2) gene expression in females. This reduction in BMPR2 may explain the higher incidence of pulmonary arterial hypertension (PAH) in women.
Area of Science:
- Endocrinology
- Cardiovascular Biology
- Molecular Genetics
Background:
- Estrogen and bone morphogenetic protein receptor type 2 (BMPR2) signaling pathways exhibit cross-talk in various organ systems.
- Pulmonary arterial hypertension (PAH) disproportionately affects females and is linked to reduced BMPR2 expression.
- Investigating the direct impact of estrogens on BMPR2 expression is crucial for understanding PAH pathogenesis.
Purpose of the Study:
- To determine if estrogens suppress BMPR2 gene expression.
- To elucidate the molecular mechanisms underlying estrogen-mediated BMPR2 regulation.
- To explore the potential contribution of this mechanism to the female predominance in PAH.
Main Methods:
- Quantitative RT-PCR and gel mobility shift assays were employed.
- Luciferase activity assays were performed in human samples, mice, and cell cultures.
- Estrogen receptor binding to the BMPR2 promoter was assessed.
Main Results:
- BMPR2 expression was lower in female human lymphocytes and mouse lungs compared to males.
- An evolutionarily conserved estrogen receptor binding site was identified in the BMPR2 promoter.
- Increased estrogen levels and estrogen receptor alpha transfection correlated with decreased BMPR2 expression.
Conclusions:
- Estrogen receptor alpha directly binds to the BMPR2 promoter, reducing its gene expression in females.
- This estrogen-induced suppression of BMPR2 may underlie the increased prevalence of PAH in females.
- Findings provide a molecular link between sex hormones and PAH development.
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