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Cancer Cell. 2005 Oct;8(4):275-85.

Global loss of imprinting leads to widespread tumorigenesis in adult mice.

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1
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, Boston, USA.

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.

PMID:
16226703
DOI:
10.1016/j.ccr.2005.09.007
[Indexed for MEDLINE]
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