Role of ERas in promoting tumour-like properties in mouse embryonic stem cells.
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.
Takahashi
Kazutoshi
K
Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Mitsui
Kaoru
K
Yamanaka
Shinya
S
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*
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)