ArticleProceedings of the National Academy of Sciences of the United States of America2010
Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Survival outcomes in endometrial cancer patients according to diabetes: a systematic review and meta-analysis.BMC cancer · 2022Pooled it
- Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.Nature communications · 2026Trial
- Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial.British journal of cancer · 2013Trial
- The emerging role of TROP2 as a diagnostic and prognostic biomarker in bladder tumor.Cancer cell international · 2026Review
- Review
- Article
- Distinguish Characters of Luminal and Glandular Epithelium from Mouse Uterus Using a Novel Enzyme-Based Separation Method.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Overview of Trop-2 in Cancer: From Pre-Clinical Studies to Future Directions in Clinical Settings.Cancers · 2023Review
- mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation.Cell death & disease · 2022Article
- Developing dietary interventions as therapy for cancer.Nature reviews. Cancer · 2022Review
- TACSTD2 upregulation is an early reaction to lung infection.Scientific reports · 2022Article
- A tissue-specific role of membrane-initiated ERα signaling for the effects of SERMs.The Journal of endocrinology · 2022Article
- Network Pharmacology-Based and Molecular Docking Analysis of Resveratrol's Pharmacological Effects on Type I Endometrial Cancer.Anti-cancer agents in medicinal chemistry · 2022Article
- Kras activation in endometrial organoids drives cellular transformation and epithelial-mesenchymal transition.Oncogenesis · 2021Article
- Two-Way Development of the Genetic Model for Endometrial Tumorigenesis in Mice: Current and Future Perspectives.Frontiers in genetics · 2021Review
- Trop2: Jack of All Trades, Master of None.Cancers · 2020Review
- Review
- Clinical and Expression Significance of AKT1 by Co-expression Network Analysis in Endometrial Cancer.Frontiers in oncology · 2019Article
- The uterine epithelial loss of Pten is inefficient to induce endometrial cancer with intact stromal Pten.PLoS genetics · 2018Article
- The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target.Oncotarget · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Epithelial-specific activation of the PI3-kinase pathway is the most common genetic alteration in type I endometrial cancer. In the majority of these tumors, PTEN expression is lost in the epithelium but maintained in tumor stroma. Currently reported PTEN knockout mouse models initiate type I endometrial cancer concomitant with loss of PTEN in both uterine epithelium and stroma. Consequently, the biologic outcome of selectively activating the PI3-kinase pathway in the endometrial epithelium remains unknown. To address this question, we established a malleable in vivo endometrial regeneration system from dissociated murine uterine epithelium and stroma. Regenerated endometrial glands responded to pharmacologic variations in hormonal milieu similar to the native endometrium. Cell-autonomous activation of the PI3-kinase pathway via biallelic loss of PTEN or activation of AKT in adult uterine epithelia in this model was sufficient to initiate endometrial carcinoma. AKT-initiated tumors were serially transplantable, demonstrating permanent genetic changes in uterine epithelia. Immunohistochemistry confirmed loss of PTEN or activation of AKT in regenerated hyperplastic glands that were surrounded by wild-type stroma. We demonstrate that cell-autonomous activation of the PI3-kinase pathway is sufficient for the initiation of endometrial carcinoma in naive adult uterine epithelia. This in vivo model provides an ideal platform for testing the response of endometrial carcinoma to targeted therapy against this common genetic alteration.
Indexed as
Identifiers
What OpenQuestion holds
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.