Evidence map›Paper›PMID 26061565›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2015

FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development.

Zhilin Liu, Yi A Ren, Stephanie A Pangas, Jaye Adams, Wei Zhou, Diego H Castrillon, Dagmar Wilhelm, JoAnne S Richards

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 82 citations in OpenAlex.

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  9. Loss ofInternational journal of molecular sciences · 2022
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  13. Non-Epithelial Ovarian Cancers: How Much Do We Really Know?International journal of environmental research and public health · 2022
    Review
  14. Article
  15. Adult-type granulosa cell tumor of the ovary.American journal of cancer research · 2022
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Zhilin LiuDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Yi A RenDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Stephanie A PangasDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Jaye AdamsDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Wei ZhouDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Diego H CastrillonDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
Dagmar WilhelmDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
JoAnne S RichardsDepartments of Molecular and Cellular Biology (Z.L., Y.A.R., S.A.P., J.A., J.S.R.), Pathology and Immunology (S.A.P.), and Obstetrics and Gynecology (J.A.), Baylor College of Medicine, and Department of Experimental Radiation Oncology (W.Z.), The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology (D.H.C.), The University of Texas Southwestern Medical School, Dallas, Texas 75390; and Department of Anatomy and Developmental Biology (D.W.), Monash University, Clayton VIC 3800, Australia.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USMonash University · AUThe University of Texas Southwestern Medical Center · US

Funding

PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MARSHALL, JOHN C · 1998 to 2013
$16.5M
Testosterone-GnRH Frequency and the Evolution of PCOS in AdolescenceP50HD028934 · NICHD · UNIVERSITY OF VIRGINIA · PI HAISENLEDER, DANIEL J. · 2014 to 2018
$8.6M
NICHD NIH HHS P50 HD028934NICHD NIH HHS U54 HD028934NICHD NIH HHS U54-HD28934
6 · The paper itself

Abstract

The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation. Coordinate depletion of the tumor suppressor Pten gene in the Foxo1/3 strain enhanced the penetrance and onset of GCT formation. Immunostaining and Western blot analyses confirmed FOXO1 and phosphatase and tensin homolog (PTEN) depletion, maintenance of globin transcription factor (GATA) 4 and nuclear localization of FOXL2 and phosphorylated small mothers against decapentaplegic (SMAD) 2/3 in the tumor cells, recapitulating results we observed in human adult GCTs. Microarray and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were suppressed. Key genes (Amh, Bmp2, and Fshr) controlling follicle growth, apoptosis, and differentiation were also suppressed. Inhbb and Grem1 were selectively elevated, whereas reduction of Inha provided additional evidence that activin signaling and small mothers against decapentaplegic (SMAD) 2/3 phosphorylation impact GCT formation. Unexpectedly, markers of Sertoli/epithelial cells (SRY [sex determining region Y]-box 9/keratin 8) and alternatively activated macrophages (chitinase 3-like 3) were elevated in discrete subpopulations within the mouse GCTs, indicating that Foxo1/3/Pten depletion not only leads to GCTs but also to altered granulosa cell fate decisions and immune responses. Thus, analyses of the Foxo1/3/Pten mouse GCTs and human adult GCTs provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of FOXL2 and GATA4, and tumor formation.

Indexed as

AdultAnimalsbeta-N-AcetylhexosaminidasesCarcinogenesisFemaleForkhead Box Protein O1Forkhead Box Protein O3Forkhead Transcription FactorsGene Expression ProfilingGene Expression Regulation, NeoplasticGonadotropinsGranulosa Cell TumorHumansImmunohistochemistryIntegrasesKeratin-8beta-N-AcetylhexosaminidasesChil3 protein, mouseCre recombinaseForkhead Box Protein O1Forkhead Box Protein O3Forkhead Transcription FactorsFOXO1 protein, humanFoxo1 protein, mouseFOXO3 protein, humanFoxO3 protein, mouseGonadotropinsIntegrasesKeratin-8LectinsPTEN PhosphohydrolaseSmad ProteinsSOX9 Transcription Factor

Identifiers

PMID26061565
PMCPMC4484779
OpenAlexW1917900907

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.