title: Nanog induces hyperplasia without initiating tumors.
abstract: Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, many contradictory reports about Nanog's involvement in tumorigenesis exist. To address this, a modified Tet-On system was utilized to generate Nanog-inducible mice. Following prolonged Nanog expression, phenotypic alterations were found to be restricted to the intestinal tract, leaving other major organs unaffected. Intestinal and colonic epithelium hyperplasia was observed-intestinal villi had doubled in length and hyperplastic epithelium outgrowths were seen after 7days. Increased proliferation of crypt cells and downregulation of the tumor suppressors Cdx2 and Klf4 was detected. ChIP analysis showed physical interaction of Nanog with the Cdx2 and Klf4 promoters, indicating a regulatory conservation from embryonic development. Despite downregulation of tumor suppressors and increased proliferation, ectopic Nanog expression did not lead to tumor formation. We conclude that unlike other pluripotency-related transcription factors, Nanog cannot be considered an oncogene.
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany; University of Münster, Faculty of Medicine, Domagstrasse 3, 48149 Münster, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Fischedick
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany; Biodonostia Health Research Institute, 20014 San Sebastián, and IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Greber
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Radstaak
authors.affiliation: University of Münster, Gerhard-Domagk-Institut for Pathology, Domagkstraße 17, 48149 Münster, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.affiliation: Center for Regenerative Therapies, Technische Universität Dresden, Tatzberg 47-51, 01307 Dresden, Germany; F. Hoffmann-La Roche, Pharma Research and Early Development Discovery Technologies, 4070 Basel, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacone
authors.affiliation: Center for Regenerative Therapies, Technische Universität Dresden, Tatzberg 47-51, 01307 Dresden, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anastassiadis
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany; University of Münster, Faculty of Medicine, Domagstrasse 3, 48149 Münster, Germany. Electronic address: office@mpi-muenster.mpg.de.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D000071317:Nanog Homeobox Protein; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins