First Author | Takahashi K | Year | 2003 |
Journal | Nature | Volume | 423 |
Issue | 6939 | Pages | 541-5 |
PubMed ID | 12774123 | Mgi Jnum | J:83823 |
Mgi Id | MGI:2663652 | Doi | 10.1038/nature01646 |
Citation | Takahashi K, et al. (2003) Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature 423(6939):541-5 |
abstractText | 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. |