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Updated: Aug 26, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens
Takahiro Kusumegi1, Junko Tanaka, Michihiro Kawano
1Endocrine Disruptors and Dioxin Research Project, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
Abstract:
A ligand-receptor pair, bone morphogenetic protein-7 (BMP7) and activin receptor IIB (actRIIB), was identified from a pool of DNA fragments recovered from MCF7 cells treated with 17beta-estradiol (E2) by chromatin immunoprecipitation with antiestrogen receptor-alphaantibody. The E2 responsiveness of both genes was confirmed in MCF cells and in the mouse uterus. Repeated treatment with E2 resulted in decreased expression of both actRIIB and BMP7 mRNA in the uteri of ovariectomized mice. A single oral administration of bisphenol A (BPA), an environmental estrogen, inhibited actRIIB and BMP7 expression and apoptosis in the luminal epithelium of the mouse uterus at diestrus (or early proestrus). This decrease, due to BPA administration, was restored by an estrogen receptor (ER) antagonist suggesting that it is mediated through ERs. These results suggest that E2 and BPA suppress estrogen-dependent apoptosis of epithelial cells of the endometrium through down-regulation of actRIIB and BMP7. Thus, we propose that BMP7 and actRIIB, a ligand-receptor pair, are involved in regulation of the apoptotic signaling pathway and might therefore be new biomarkers of the effects of environmental estrogens on the female reproductive tract.
Insights
17beta-estradiol (E2) and environmental estrogens like bisphenol A (BPA) suppress endometrial cell apoptosis by down-regulating bone morphogenetic protein-7 (BMP7) and activin receptor IIB (actRIIB) via estrogen receptors (ERs). These genes may serve as biomarkers for environmental estrogen effects.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Estrogen receptor (ER) signaling plays a critical role in regulating female reproductive tract tissues.
- Environmental estrogens, such as bisphenol A (BPA), can disrupt normal endocrine functions.
- Apoptosis, or programmed cell death, is a crucial process in endometrial tissue homeostasis.
Purpose of the Study:
- To identify novel genes regulated by 17beta-estradiol (E2) in MCF7 cells.
- To investigate the role of identified genes in E2- and BPA-mediated effects on uterine apoptosis.
- To explore potential biomarkers for environmental estrogen exposure.
Main Methods:
- Chromatin immunoprecipitation (ChIP) coupled with DNA recovery from E2-treated MCF7 cells.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) to assess mRNA expression in MCF cells and mouse uteri.
- Administration of E2, BPA, and an ER antagonist to ovariectomized mice to evaluate gene expression and apoptosis.
Main Results:
- A novel ligand-receptor pair, bone morphogenetic protein-7 (BMP7) and activin receptor IIB (actRIIB), was identified as E2-responsive.
- Both E2 and BPA treatment led to decreased expression of actRIIB and BMP7 mRNA in the mouse uterus.
- BPA-induced inhibition of actRIIB and BMP7 expression and apoptosis was reversed by an ER antagonist, indicating ER mediation.
- E2 and BPA were found to suppress estrogen-dependent apoptosis in endometrial epithelial cells through down-regulation of actRIIB and BMP7.
Conclusions:
- BMP7 and actRIIB are involved in the regulation of apoptotic signaling pathways in the female reproductive tract.
- E2 and BPA suppress endometrial epithelial cell apoptosis via down-regulation of BMP7 and actRIIB through ERs.
- BMP7 and actRIIB may serve as novel biomarkers for assessing the impact of environmental estrogens on the female reproductive system.
