| First Author | Holm TM | Year | 2005 |
| Journal | Cancer Cell | Volume | 8 |
| Issue | 4 | Pages | 275-85 |
| PubMed ID | 16226703 | Mgi Jnum | J:104860 |
| Mgi Id | MGI:3612925 | Doi | 10.1016/j.ccr.2005.09.007 |
| Citation | Holm TM, et al. (2005) Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell 8(4):275-85 |
| abstractText | 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. |
