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. 2005 Oct;8(4):275-85.
doi: 10.1016/j.ccr.2005.09.007.

Global loss of imprinting leads to widespread tumorigenesis in adult mice

Teresa M Holm  1 , Laurie Jackson-Grusby, Tobias Brambrink, Yasuhiro Yamada, William M Rideout 3rd, Rudolf Jaenisch
Affiliations
Free article

Global loss of imprinting leads to widespread tumorigenesis in adult mice

Teresa M Holm et al. Cancer Cell. 2005 Oct.
Free article

Erratum in

  • Cancer Cell. 2005 Nov;8(5):433
  • Cancer Cell. 2006 Jan;9(1):69

Abstract

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 TGFbeta 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.

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