Related Experiment Video
Updated: Feb 17, 2026
Author Spotlight: Advancing Human Ovarian Repair and Cancer Studies with Surface Epithelium Organoids
Published on: August 16, 2024
17β-Estradiol sensitizes ovarian surface epithelium to transformation by suppressing Disabled-2 expression
Nhung H Vuong1,2, Omar Salah Salah2, Barbara C Vanderhyden3,4
1Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
Abstract:
Estrogen replacement therapy increases the risk of human ovarian cancer and exogenous estradiol accelerates the onset of ovarian cancer in mouse models. This study uses primary cultures of mouse ovarian surface epithelium (OSE) to demonstrate that one possible mechanism by which estrogen accelerates the initiation of ovarian cancer is by up-regulation of microRNA-378 via the ESR1 pathway to result in the down-regulation of a tumour suppressor called Disabled-2 (Dab2). Estrogen suppression of Dab2 was reproducible in vivo and across many cell types including mouse oviductal epithelium and primary cultures of human ovarian cancer cells. Suppression of Dab2 resulted in increased proliferation, loss of contact inhibition, morphological dysplasia, and resistance to oncogene-induced senescence - all factors that can sensitize OSE to transformation. Given that DAB2 is highly expressed in healthy human OSE and is absent in the majority of ovarian tumours, this study has taken the first steps to provide a mechanistic explanation for how estrogen therapy may play a role in the initiation of ovarian cancer.
Insights
Estrogen therapy may accelerate ovarian cancer by increasing microRNA-378, which suppresses the tumor suppressor Disabled-2 (Dab2). This mechanism was observed in mouse ovarian cells and human ovarian cancer cells, highlighting estrogen
Area of Science:
- Molecular Biology
- Oncology
- Endocrinology
Background:
- Estrogen replacement therapy is linked to increased ovarian cancer risk.
- Exogenous estradiol accelerates ovarian cancer in mouse models.
- The precise mechanisms by which estrogen influences ovarian cancer initiation require further elucidation.
Purpose of the Study:
- To investigate the role of estrogen in ovarian cancer initiation.
- To identify molecular pathways through which estrogen may promote ovarian tumorigenesis.
- To examine the regulation of the tumor suppressor Disabled-2 (Dab2) by estrogen.
Main Methods:
- Primary cultures of mouse ovarian surface epithelium (OSE) were utilized.
- The ESR1 pathway and microRNA-378 (miR-378) were investigated in relation to estrogen.
- In vivo studies and experiments with other cell types, including human ovarian cancer cells, were performed.
Main Results:
- Estrogen up-regulates miR-378 via the ESR1 pathway, leading to down-regulation of the tumor suppressor Dab2.
- Estrogen-induced suppression of Dab2 was observed in mouse OSE, oviductal epithelium, and human ovarian cancer cells.
- Dab2 suppression resulted in increased cell proliferation, loss of contact inhibition, dysplasia, and resistance to senescence.
Conclusions:
- Estrogen may accelerate ovarian cancer initiation by suppressing Dab2 through the miR-378/ESR1 pathway.
- The down-regulation of Dab2, a tumor suppressor highly expressed in healthy OSE but absent in tumors, is a key finding.
- This study provides a mechanistic link between estrogen therapy and ovarian cancer initiation, suggesting Dab2 as a critical factor.
