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

Nature. 2003 May 29;423(6939):541-5. doi: 10.1038/nature01646.

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.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cell Transformation, Neoplastic*
  • Cloning, Molecular
  • Embryo, Mammalian / metabolism*
  • Embryo, Mammalian / pathology*
  • Genes, ras / genetics
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Mice
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Oncogene Protein p21(ras) / chemistry
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Pseudogenes / genetics
  • Stem Cells / metabolism*
  • Stem Cells / pathology*

Substances

  • ERas protein, human
  • ERas protein, mouse
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-raf
  • Oncogene Protein p21(ras)

Associated data

  • GENBANK/AB093573
  • GENBANK/AB093575