ArticlePLoS genetics2018
The uterine epithelial loss of Pten is inefficient to induce endometrial cancer with intact stromal Pten.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Generation and Characterization of a Rdh1-iCre Line to Study Uterine Glandular Biology.Genesis (New York, N.Y. : 2000) · 2026Article
- Co-mutations of CTNNB1 and PTEN drive aggressive tumor progression in endometrial cancer.Disease models & mechanisms · 2026Article
- TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ob/ob obese mice promote tumorigenesis of endometrial cancer associated with Pten deficiency.Endocrine-related cancer · 2025Article
- GRB2 regulation of essential signaling pathways in the endometrium is critical for implantation and decidualization.Nature communications · 2025Article
- Tumor suppressor genes in the tumor microenvironment.Disease models & mechanisms · 2025Review
- Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment.Cancers · 2024Review
- Androgen-responsive FOXP4 is a target for endometrial carcinoma.Communications biology · 2024Article
- In Vivo Intra-Uterine Delivery of TAT-Fused Cre Recombinase and CRISPR/Cas9 Editing System in Mice Unveil Histopathology of Pten/p53-Deficient Endometrial Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Transient and DNA-free in vivo CRISPR/Cas9 genome editing for flexible modeling of endometrial carcinogenesis.Cancer communications (London, England) · 2023Article
- Structural and functional changes in rat uterus induced by neonatal androgenization.Journal of molecular histology · 2022Article
- FOXA2 suppresses endometrial carcinogenesis and epithelial-mesenchymal transition by regulating enhancer activity.The Journal of clinical investigation · 2022Article
- Canonical TGFβ Signaling and Its Contribution to Endometrial Cancer Development and Progression-Underestimated Target of Anticancer Strategies.Journal of clinical medicine · 2021Review
- Kras activation in endometrial organoids drives cellular transformation and epithelial-mesenchymal transition.Oncogenesis · 2021Article
- Different Cre systems induce differential microRNA landscapes and abnormalities in the female reproductive tracts of Dgcr8 conditional knockout mice.Cell proliferation · 2021Article
- Two-Way Development of the Genetic Model for Endometrial Tumorigenesis in Mice: Current and Future Perspectives.Frontiers in genetics · 2021Review
- Cancer-associated mutations in normal human endometrium: Surprise or expected?Cancer science · 2020Review
- Emerging role of PTEN loss in evasion of the immune response to tumours.British journal of cancer · 2020Review
- Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Mutation of the tumor suppressor Pten often leads to tumorigenesis in various organs including the uterus. We previously showed that Pten deletion in the mouse uterus using a Pgr-Cre driver (Ptenf/fPgrCre/+) results in rapid development of endometrial carcinoma (EMC) with full penetration. We also reported that Pten deletion in the stroma and myometrium using Amhr2-Cre failed to initiate EMC. Since the Ptenf/fPgrCre/+ uterine epithelium was primarily affected by tumorigenesis despite its loss in both the epithelium and stroma, we wanted to know if Pten deletion in epithelia alone will induce tumorigenesis. We found that mice with uterine epithelial loss of Pten under a Ltf-iCre driver (Ptenf/f/LtfCre/+) develop uterine complex atypical hyperplasia (CAH), but rarely EMC even at 6 months of age. We observed that Ptenf/fPgrCre/+ uteri exhibit a unique population of cytokeratin 5 (CK5) and transformation related protein 63 (p63)-positive epithelial cells; these cells mark stratified epithelia and squamous differentiation. In contrast, Ptenf/fLtfCre/+ hyperplastic epithelia do not undergo stratification, but extensive epithelial cell apoptosis. This increased apoptosis is associated with elevation of TGFβ levels and activation of downstream effectors, SMAD2/3 in the uterine stroma. Our results suggest that stromal PTEN via TGFβ signaling restrains epithelial cell transformation from hyperplasia to carcinoma. In conclusion, this study, using tissue-specific deletion of Pten, highlights the epithelial-mesenchymal cross-talk in the genesis of endometrial carcinoma.
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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.