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Updated: Aug 19, 2025
Ovarian Tissue Culture to Visualize Phenomena in Mouse Ovary
Published on: June 19, 2018
Loss of Runx1 Induces Granulosa Cell Defects and Development of Ovarian Tumors in the Mouse
Kamiya Bridges1, Humphrey H-C Yao1, Barbara Nicol1
1Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Abstract:
Genetic alterations of the RUNX1 gene are associated with a variety of malignancies, including female-related cancers. The role of RUNX1 as either a tumor suppressor gene or an oncogene is tissue-dependent and varies based on the cancer type. Both the amplification and deletion of the RUNX1 gene have been associated with ovarian cancer in humans. In this study, we investigated the effects of Runx1 loss on ovarian pathogenesis in mice. A conditional loss of Runx1 in the somatic cells of the ovary led to an increased prevalence of ovarian tumors in aged mice. By the age of 15 months, 27% of Runx1 knockout (KO) females developed ovarian tumors that presented characteristics of granulosa cell tumors. While ovaries from young adult mice did not display tumors, they all contained abnormal follicle-like lesions. The granulosa cells composing these follicle-like lesions were quiescent, displayed defects in differentiation and were organized in a rosette-like pattern. The RNA-sequencing analysis further revealed differentially expressed genes in Runx1 KO ovaries, including genes involved in metaplasia, ovarian cancer, epithelial cell development, tight junctions, cell-cell adhesion, and the Wnt/beta-catenin pathway. Together, this study showed that Runx1 is required for normal granulosa cell differentiation and prevention of ovarian tumor development in mice.
Insights
RUNX1 loss in mice causes ovarian tumors, specifically granulosa cell tumors. This gene is crucial for normal ovarian granulosa cell differentiation and preventing ovarian cancer development.
Area of Science:
- Genetics
- Oncology
- Reproductive Biology
Background:
- RUNX1 gene alterations are linked to various cancers, including ovarian cancer.
- RUNX1's function as a tumor suppressor or oncogene is context-dependent.
- Both gene amplification and deletion of RUNX1 are implicated in human ovarian cancer.
Purpose of the Study:
- To investigate the impact of RUNX1 loss on ovarian pathogenesis in a mouse model.
- To understand RUNX1's role in ovarian granulosa cell differentiation and tumor suppression.
Main Methods:
- Conditional knockout of Runx1 in ovarian somatic cells of mice.
- Histopathological analysis of ovaries from young and aged Runx1 knockout mice.
- RNA-sequencing analysis of Runx1 knockout ovaries.
Main Results:
- Conditional loss of Runx1 in ovarian somatic cells increased ovarian tumor prevalence in aged mice (27% by 15 months).
- Ovarian tumors exhibited characteristics of granulosa cell tumors.
- Abnormal follicle-like lesions with quiescent, undifferentiated granulosa cells in a rosette pattern were observed in young adult mice.
- RNA-sequencing identified differential gene expression related to metaplasia, ovarian cancer, epithelial development, cell adhesion, and Wnt/beta-catenin signaling.
Conclusions:
- RUNX1 is essential for normal granulosa cell differentiation in the ovary.
- RUNX1 plays a critical role in preventing ovarian tumor development.
- RUNX1 loss disrupts pathways involved in ovarian cancer pathogenesis.
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