ArticleOncotarget2016
Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Age-related meningeal extracellular matrix remodeling compromises CNS lymphatic function.Journal of neuroinflammation · 2025Article
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- Lineage tracing of mutant granulosa cells reveals in vivo protective mechanisms that prevent granulosa cell tumorigenesis.Cell death and differentiation · 2023Article
- Role of EZH2 in Uterine Gland Development.International journal of molecular sciences · 2022Article
- Transcriptomic Profiling of Gene Expression Associated with Granulosa Cell Tumor Development in a Mouse Model.Cancers · 2022Article
- New insights into testicular granulosa cell tumors.Oncology letters · 2020Review
- Ski mediates TGF-β1-induced fibrosarcoma cell proliferation and promotes tumor growth.Journal of Cancer · 2020Article
- Structural biology of the TGFβ family.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression.BMC cancer · 2019Article
- Differential isoform expression and alternative splicing in sex determination in mice.BMC genomics · 2019Article
- Tumor-suppressive signaling in the uterus.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Genes responsible for proliferation, differentiation, and junction adhesion are significantly up-regulated in human ovarian granulosa cells during a long-term primary in vitro culture.Histochemistry and cell biology · 2019Article
- A novel mouse model of testicular granulosa cell tumors.Molecular human reproduction · 2018Article
- Disruption of postnatal folliculogenesis and development of ovarian tumor in a mouse model with aberrant transforming growth factor beta signaling.Reproductive biology and endocrinology : RB&E · 2017Article
- Conditional abrogation of transforming growth factor-β receptor 1 in PTEN-inactivated endometrium promotes endometrial cancer progression in mice.The Journal of pathology · 2017Article
- Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRASCellular and molecular gastroenterology and hepatology · 2017Article
- SMAD3 Activation: A Converging Point of Dysregulated TGF-Beta Superfamily Signaling and Genetic Aberrations in Granulosa Cell Tumor Development?Biology of reproduction · 2016Review
- Activin receptor-like kinases: a diverse family playing an important role in cancer.American journal of cancer research · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.