Genetic Inactivation of Notch1 Synergizes with Loss of Trp53 to Induce Tumor Formation in the Adult Mouse Forebrain.

ABSTRACT: Simultaneous genetic inactivation of the key Notch signaling mediator RBP-Jk and p53 leads to the formation of forebrain tumors in mice, suggesting a tumor suppressor role of the Notch pathway in this context. However, the contribution of individual Notch receptors to the tumor-suppressive activity of Notch signaling in the brain remains elusive. Here, we show that simultaneous Notch1 and Notch2 deletion, similar to complete ablation of canonical Notch signaling by Rbpj inactivation, cooperates with Trp53 deletion to promote tumor growth in the adult forebrain. We also demonstrate that inactivation of Notch1 and Trp53 in cells with active Notch signaling is sufficient to induce brain tumor or hyperplasia formation. Analysis of tumor location sugges

SUBMITTER: Parmigiani E 

PROVIDER: S-EPMC9655454 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature