title: Role of ERas in promoting tumour-like properties in mouse embryonic stem cells.
abstract: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. Their immortality and rapid growth make them attractive sources for stem cell therapies; however, they produce tumours (teratomas) when transplanted, which could preclude their therapeutic usage. Why ES cells, which lack chromosomal abnormalities, possess tumour-like properties is largely unknown. Here we show that mouse ES cells specifically express a Ras-like gene, which we have named ERas. We show that human HRasp, which is a recognized pseudogene, does not contain reported base substitutions and instead encodes the human orthologue of ERas. This protein contains amino-acid residues identical to those present in active mutants of Ras and causes oncogenic transformation in NIH 3T3 cells. ERas interacts with phosphatidylinositol-3-OH kinase but not with Raf. ERas-null ES cells maintain pluripotency but show significantly reduced growth and tumorigenicity, which are rescued by expression of ERas complementary DNA or by activated phosphatidylinositol-3-OH kinase. We conclude that the transforming oncogene ERas is important in the tumour-like growth properties of ES cells.
authors.affiliation: Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mitsui
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology*; D011905:Genes, ras / Q000235:genetics; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D015689:Oncogene Protein p21(ras) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011544:Pseudogenes / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: C474774:ERas protein, human; C474773:ERas protein, mouse; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D015689:Oncogene Protein p21(ras)