A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis
Open accessAbstract
Endometriosis is considered to be an estrogen-dependent inflammatory disease, but its etiology is unclear. Thus far, a mechanistic role for steroid receptor coactivators (SRCs) in the progression of endometriosis has not been elucidated. An SRC-1-null mouse model reveals that the mouse SRC-1 gene has an essential role in endometriosis progression. Notably, a previously unidentified 70-kDa SRC-1 proteolytic isoform is highly elevated both in the endometriotic tissue of mice with surgically induced endometriosis and in endometriotic stromal cells biopsied from patients with endometriosis compared to normal endometrium. Tnf⁻/⁻ and Mmp9⁻/⁻ mice with surgically induced endometriosis showed that activation of tumor necrosis factor a (TNF-α)-induced matrix metallopeptidase 9 (MMP9) activity mediates formation of the 70-kDa SRC-1 C-terminal isoform in endometriotic mouse tissue. In contrast to full-length SRC-1, the endometriotic 70-kDa SRC-1 C-terminal fragment prevents TNF-α-mediated apoptosis in human endometrial epithelial cells and causes the epithelial-mesenchymal transition and the invasion of human endometrial cells that are hallmarks of progressive endometriosis. Collectively, the newly identified TNF-α-MMP9-SRC-1 isoform functional axis promotes pathogenic progression of endometriosis.
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It is becoming increasingly evident that altered expression of genes in a pathological context contributes to many of the biological processes that are dysregulated in endometriosis, including cell proliferation, inhibition of apoptosis, and altered hormonal sensitivity.
“It is becoming increasingly evident that altered expression of genes in a pathological context contributes to many of the biological processes that are dysregulated in endometriosis, including cell proliferation, inhibition of apoptosis, and altered hormonal sensitivity.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
The endometriotic 70-kDa SRC-1 C-terminal fragment prevents TNF-a-mediated apoptosis in human endometrial epithelial cells and causes the epithelial-mesenchymal transition and the invasion of human endometrial cells that are hallmarks of progressive endometriosis.
“In contrast to full-length SRC-1, the endometriotic 70-kDa SRC-1 C-terminal fragment prevents TNF-a-mediated apoptosis in human endometrial epithelial cells and causes the epithelial-mesenchymal transition and the invasion of human endometrial cells that are hallmarks of progressive endometriosis.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
A steroid receptor coactivator-1 (SRC-1)-null mouse model reveals that the mouse SRC-1 gene has an essential role in endometriosis progression.
“A steroid receptor coactivator-1 (SRC-1)-null mouse model reveals that the mouse SRC-1 gene has an essential role in endometriosis progression.111”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
A 70-kDa SRC-1 proteolytic isoform is highly elevated both in the endometriotic tissue of mice with surgically induced endometriosis and in endometriotic stromal cells biopsied from patients with endometriosis compared to normal endometrium.
“A 70-kDa SRC-1 proteolytic isoform is highly elevated both in the endometriotic tissue of mice with surgically induced endometriosis and in endometriotic stromal cells biopsied from patients with endometriosis compared to normal endometrium.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
The newly identified SRC-1 isoform functional axis promotes pathogenic progression of endometriosis.
“The newly identified SRC-1 isoform functional axis promotes pathogenic progression of endometriosis.111”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
Studies focused on gene regulation using transgenic models will provide valuable insights into mechanisms that may contribute to endometriosis.
“Thus, studies focused on gene regulation using transgenic models will provide valuable insights into mechanisms that may contribute to endometriosis.116,117,111”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [111]
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- Authors
- Han, S. J., Hawkins, S. M., Begum, K., Jung, S. Y., Kovanci, E., Qin, J., Lydon, J. P., DeMayo, F. J., & O'Malley, B. W.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Venue
- Nature Medicine
- Published
- 2012-06-03
- Volume
- 18
- Issue
- 7
- Pages
- 1102-1111
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3541027
- OpenAlex
- W1975412389
- Cited by
- 149
- References
- 46
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 8 · 2016: 7 · 2015: 14 · 2014: 21 · 2013: 9 · 2012: 4
- FWCI
- 17.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA077530, R01 CA077030)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK059820)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54 HD-0077495, P30HD007495, U54HD007495, R03HD077495, K12HD050128, R01HD008188, R01HD007857)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, SRC-1, TNF signaling, MMP-9, apoptosis, epithelial-mesenchymal transition, etanercept, estrogen receptor coactivator, endometriotic stromal cells
- MeSH terms
- Animals, Choristoma, Endometriosis, Endometrium, Female, Humans, Mice, Inbred C57BL, Molecular Weight, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Cell Death, Disease Progression, Protein Isoforms, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mice, Nuclear Receptor Coactivator 1, Epithelial-Mesenchymal Transition
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