title: Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production.
abstract: The tumor suppressor gene PTEN, which is frequently mutated in human cancers, encodes a lipid phosphatase for phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] and antagonizes phosphatidylinositol 3 kinase. Primordial germ cells (PGCs), which are the embryonic precursors of gametes, are the source of testicular teratoma. To elucidate the intracellular signaling mechanisms that underlie germ cell differentiation and proliferation, we have generated mice with a PGC-specific deletion of the Pten gene. Male mice that lacked PTEN exhibited bilateral testicular teratoma, which resulted from impaired mitotic arrest and outgrowth of cells with immature characters. Experiments with PTEN-null PGCs in culture revealed that these cells had greater proliferative capacity and enhanced pluripotent embryonic germ (EG) cell colony formation. PTEN appears to be essential for germ cell differentiation and an important factor in testicular germ cell tumor formation.
authors.affiliation: Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yomogida
authors.forename: Hilda
authors.initials: H
authors.lastname: Lomeli
authors.forename: Noriko
authors.initials: N
authors.lastname: Asada
authors.forename: Megumi
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013724:Teratoma / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000473:pathology / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human