Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/21/5409 |
| _version_ | 1797468808403746816 |
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| author | Elena Parmigiani Claudio Giachino |
| author_facet | Elena Parmigiani Claudio Giachino |
| author_sort | Elena Parmigiani |
| collection | DOAJ |
| description | 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 <i>Notch1</i> and <i>Notch2</i> deletion, similar to complete ablation of canonical Notch signaling by <i>Rbpj</i> inactivation, cooperates with <i>Trp53</i> deletion to promote tumor growth in the adult forebrain. We also demonstrate that inactivation of <i>Notch1</i> and <i>Trp53</i> in cells with active Notch signaling is sufficient to induce brain tumor or hyperplasia formation. Analysis of tumor location suggests a multifocal origin and shows that ventral forebrain regions and olfactory bulbs are the most affected sites. Hence, Notch1 cooperates with p53 to repress malignant transformation in the adult mouse forebrain. |
| first_indexed | 2024-03-09T19:12:37Z |
| format | Article |
| id | doaj.art-d4be9505e65a48e386cbdfbc138fcd0d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:12:37Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d4be9505e65a48e386cbdfbc138fcd0d2023-11-24T04:03:57ZengMDPI AGCancers2072-66942022-11-011421540910.3390/cancers14215409Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse ForebrainElena Parmigiani0Claudio Giachino1Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandEmbryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, SwitzerlandSimultaneous 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 <i>Notch1</i> and <i>Notch2</i> deletion, similar to complete ablation of canonical Notch signaling by <i>Rbpj</i> inactivation, cooperates with <i>Trp53</i> deletion to promote tumor growth in the adult forebrain. We also demonstrate that inactivation of <i>Notch1</i> and <i>Trp53</i> in cells with active Notch signaling is sufficient to induce brain tumor or hyperplasia formation. Analysis of tumor location suggests a multifocal origin and shows that ventral forebrain regions and olfactory bulbs are the most affected sites. Hence, Notch1 cooperates with p53 to repress malignant transformation in the adult mouse forebrain.https://www.mdpi.com/2072-6694/14/21/5409Notch signalingbrain tumorRbpjneural progenitorforebraintumor suppressor |
| spellingShingle | Elena Parmigiani Claudio Giachino Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain Cancers Notch signaling brain tumor Rbpj neural progenitor forebrain tumor suppressor |
| title | Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain |
| title_full | Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain |
| title_fullStr | Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain |
| title_full_unstemmed | Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain |
| title_short | Genetic Inactivation of <i>Notch1</i> Synergizes with Loss of <i>Trp53</i> to Induce Tumor Formation in the Adult Mouse Forebrain |
| title_sort | genetic inactivation of i notch1 i synergizes with loss of i trp53 i to induce tumor formation in the adult mouse forebrain |
| topic | Notch signaling brain tumor Rbpj neural progenitor forebrain tumor suppressor |
| url | https://www.mdpi.com/2072-6694/14/21/5409 |
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