| First Author | Lasorella A | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 9 | Pages | 3563-74 |
| PubMed ID | 15831462 | Mgi Jnum | J:97629 |
| Mgi Id | MGI:3575959 | Doi | 10.1128/MCB.25.9.3563-3574.2005 |
| Citation | Lasorella A, et al. (2005) Id2 mediates tumor initiation, proliferation, and angiogenesis in rb mutant mice. Mol Cell Biol 25(9):3563-74 |
| abstractText | The inhibitor of differentiation Id2 is a target of the retinoblastoma (Rb) protein during mouse embryogenesis. In Rb(+/-) mice, LOH at the wild-type Rb allele initiates pituitary adenocarcinoma, a tumor derived from embryonic melanotropes. Here we identify a critical role for Id2 in initiation, growth, and angiogenesis of pituitary tumors from Rb(+/-) mice. We show that proliferation and differentiation are intimately coupled in Rb(+/-) pituitary cells before tumor initiation. In Id2-null pituitaries, premature activation of basic helix-loop-helix-mediated transcription and expression of the cdk inhibitor p27(Kip1) impairs the proliferation of melanotropes and tumor initiation. Without Id2, Rb(+/-) mice have fewer early tumor lesions and a markedly decreased proliferation rate of the tumor foci. Expression of Id2 by pituitary tumor cells promotes growth and angiogenesis by functioning as a master regulator of vascular endothelial growth factor (VEGF). In human neuroblastoma, the N-Myc-driven expression of Id2 is sufficient and necessary for expression of VEGF. These results establish that aberrant Id2 activity directs initiation and progression of embryonal cancer. |
