Role of ERas in promoting tumour-like properties in mouse embryonic stem cells

Article

关键词: PHOSPHATIDYLINOSITOL 3-KINASE;    PROTEIN;    KINASE;    TRANSFORMATION;    GENE;    AKT;    ESTABLISHMENT;    SUPPRESSION;    PTEN;    LINE;   

DOI  :  10.1038/nature01646

来源: SCIE

【 摘 要 】

Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos(1,2). Their immortality and rapid growth make them attractive sources for stem cell therapies(3); however, they produce tumours (teratomas) when transplanted, which could preclude their therapeutic usage(4). 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(5) and causes oncogenic transformation in NIH 3T3 cells. ERas interacts with phosphatidylinositol-3-OH kinase(6) but not with Raf(7,8). 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.

【 授权许可】

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