ArticleGenes & development2015
Noncatalytic PTEN missense mutation predisposes to organ-selective cancer development in vivo.
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Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Impaired nuclear PTEN function drives macrocephaly, lymphadenopathy and late-onset cancer in PTEN hamartoma tumour syndrome.Disease models & mechanisms · 2026Article
- Developmental estrogen exposure in mice disrupts uterine epithelial cell differentiation and causes adenocarcinoma via Wnt/β-catenin and PI3K/AKT signaling.PLoS biology · 2023Article
- Hyperphosphorylated PTEN exerts oncogenic properties.Nature communications · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- Non-phosphorylatable cyclin D1 mutant potentiates endometrial hyperplasia and drives carcinoma with Pten loss.Oncogene · 2022Article
- Mouse model and human patient data reveal critical roles for Pten and p53 in suppressing POLE mutant tumor development.NAR cancer · 2022Article
- Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma.Neoplasia (New York, N.Y.) · 2020Article
- PTEN as a Guardian of the Genome: Pathways and Targets.Cold Spring Harbor perspectives in medicine · 2020Review
- Tagging enhances histochemical and biochemical detection of Ran Binding Protein 9 in vivo and reveals its interaction with Nucleolin.Scientific reports · 2020Article
- PTEN Mouse Models of Cancer Initiation and Progression.Cold Spring Harbor perspectives in medicine · 2020Review
- Acrylamide induces HepG2 cell proliferation through upregulation of miR-21 expression.Journal of biomedical research · 2019Article
- Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer.Nature communications · 2019Article
- Personal Mutanomes Meet Modern Oncology Drug Discovery and Precision Health.Pharmacological reviews · 2019Review
- Regulation of PTEN expression by noncoding RNAs.Journal of experimental & clinical cancer research : CR · 2018Review
- Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation.Familial cancer · 2018Article
- Article
- PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex.eLife · 2017Article
- RCAN1-4 is a thyroid cancer growth and metastasis suppressor.JCI insight · 2017Article
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Authors and funding
37 authors at 5 institutions in 2 countries.
Enrico CasertaSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Onur EgribozSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Hui WangSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Chelsea MartinSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Christopher KoivistoSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Thierry PecótSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Raleigh D KladneySolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Changxian ShenSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Kang-Sup ShimSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Thac PhamSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Matthew K KarikomiSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Melissa J MauntelSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Sarmila MajumderSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Maria C CuitinoSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Xing TangSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Arunima SrivastavaSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Lianbo YuCenter for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA; Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Julie WallaceSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Xiaokui MoCenter for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA; Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Morag ParkDepartment of Biochemistry, McGill University, Montreal, Quebec H3A 1A1, Canada; Rosalind and Morris Goodman Cancer Center, McGill University, Montreal, Quebec H3A 1A1, Canada; Department of Oncology, McGill University, Montreal, Quebec H3A 1A1, Canada;
Soledad A FernandezCenter for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA; Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Robert PilarskiDepartment of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA;
Krista M D La PerleDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Thomas J RosolDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Vincenzo CoppolaSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Diego H CastrillonDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
Cynthia TimmersSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA;
David E CohnDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA;
David M O'MalleyDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA;
Floor BackesDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA;
Adrian A SuarezDepartment of Pathology, The Ohio State University, Columbus, Ohio 43210, USA;
Paul GoodfellowDepartment of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA;
Helen M ChamberlinDepartment of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA;
Erin R MacraeDivision of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Charles L ShapiroDivision of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Michael C OstrowskiSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
Gustavo LeoneSolid Tumor Biology Program, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Genetics, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA; Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA;
The Ohio State University · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USOhio State University Hospital · USMcGill University · CAThe University of Texas Southwestern Medical Center · US
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MSuppression of Mammary Tumorigenesis by Stromal p53P01CA097189 · NCI · OHIO STATE UNIVERSITY · PI FERNANDEZ, SOLEDAD A · 2004 to 2016
$16.1MTumor Suppressor Roles of E2F7 & E2F8 in Hepatocellular Carcinoma (HCC)R01CA121275 · NCI · OHIO STATE UNIVERSITY · PI LEONE, GUSTAVO WALTER · 2008 to 2018
$3.1MMouse Pathobiology: Models of Human DiseaseT32OD010429 · OD · OHIO STATE UNIVERSITY · PI NIEWIESK, STEFAN, OGLESBEE, MICHAEL J · 2012 to 2017
$1.3MNCI NIH HHS P01 CA097189NCI NIH HHS P01 CA97189NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA121275NCI NIH HHS R01CA121275NIH HHS T32 OD010429
Abstract
Inactivation of phosphatase and tensin homology deleted on chromosome 10 (PTEN) is linked to increased PI3K-AKT signaling, enhanced organismal growth, and cancer development. Here we generated and analyzed Pten knock-in mice harboring a C2 domain missense mutation at phenylalanine 341 (Pten(FV)), found in human cancer. Despite having reduced levels of PTEN protein, homozygous Pten(FV/FV) embryos have intact AKT signaling, develop normally, and are carried to term. Heterozygous Pten(FV/+) mice develop carcinoma in the thymus, stomach, adrenal medulla, and mammary gland but not in other organs typically sensitive to Pten deficiency, including the thyroid, prostate, and uterus. Progression to carcinoma in sensitive organs ensues in the absence of overt AKT activation. Carcinoma in the uterus, a cancer-resistant organ, requires a second clonal event associated with the spontaneous activation of AKT and downstream signaling. In summary, this PTEN noncatalytic missense mutation exposes a core tumor suppressor function distinct from inhibition of canonical AKT signaling that predisposes to organ-selective cancer development in vivo.
Indexed as
Signal TransductionAnimalsCarcinomaCell NucleusCells, CulturedEmbryo, MammalianEnzyme ActivationFemaleGene Knock-In TechniquesMiceMutation, MissenseOncogene Protein v-aktProtein StabilityPTEN PhosphohydrolaseOncogene Protein v-aktPTEN PhosphohydrolasebreastcancerendometriumF341Vptenuterus
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