Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin-specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model by using transient demethylation to generate imprint-free mouse embryonic stem cells (IF-ES cells). Embryonic fibroblasts derived from IF-ES cells (IF-MEFs) display TGF beta resistance and reduced p19 and p53 expression and form tumors in SCID mice. IF-MEFs exhibit spontaneous immortalization and cooperate with H-Ras in cellular transformation. Chimeric animals derived from IF-ES cells develop multiple tumors arising from the injected IF-ES cells within 12 months. These data demonstrate that LOI alone can predispose cells to tumorigenesis and identify a pathway through which immortality conferred by LOI lowers the threshold for transformation.
机构:
Univ Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, CanadaUniv Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, Canada
Baqir, S
Smith, LC
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机构:
Univ Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, CanadaUniv Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, Canada
机构:
Univ Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, CanadaUniv Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, Canada
Baqir, S
Smith, LC
论文数: 0引用数: 0
h-index: 0
机构:
Univ Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, CanadaUniv Montreal, Fac Vet Med, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6, Canada