Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas
The Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are der...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608801492 |
| _version_ | 1811266023765049344 |
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| author | Gilson S. Baia Stefano Stifani Edna T. Kimura Michael W. McDermott Russell O. Pieper Anita Lal |
| author_facet | Gilson S. Baia Stefano Stifani Edna T. Kimura Michael W. McDermott Russell O. Pieper Anita Lal |
| author_sort | Gilson S. Baia |
| collection | DOAJ |
| description | The Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are deregulated in meningiomas. How-ever, the functional consequence of abnormal Notch signaling to meningiomas is unknown. Here, we report that exogenous expression of the Notch pathway effector, HES1, is associated with tetraploid cells in meningioma cell lines. Activated Notch1 and Notch2 receptors induced endogenous HES1 expression and were associated with tetraploidy in meningiomas. Tetraploid meningioma cells exhibited nuclear features of chromosomal instability and increased frequency of nuclear atypia, such as multipolar mitotic spindles and accumulation of cells with large nuclei. FACS-sorted tetraploid cells are viable but have higher rates of spontaneous apoptosis when compared with diploid cells. We have used spectral karyotyping to show that, in contrast to diploid cells, tetraploid cells develop a higher number of both numerical and structural chromosomal abnormalities. Our findings identify a novel function for the Notch signaling pathway in generating tetraploidy and contributing to chromosomal instability. We speculate that abnormal Notch signaling pathway is an initiating genetic mechanism for meningioma and potentially promotes tumor development. |
| first_indexed | 2024-04-12T20:35:42Z |
| format | Article |
| id | doaj.art-16d64700389d4e06a497f2288466fcdd |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T20:35:42Z |
| publishDate | 2008-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-16d64700389d4e06a497f2288466fcdd2022-12-22T03:17:36ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-06-0110660461210.1593/neo.08356Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in MeningiomasGilson S. Baia0Stefano Stifani1Edna T. Kimura2Michael W. McDermott3Russell O. Pieper4Anita Lal5Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco CA 94143 USACenter for Neuronal Survival, Montreal Neurological Institute, McGill University Montreal Quebec Canada H3A 2B4Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Av Prof Lineu Prestes 1524 05508-000 Sao Paulo SP BrazilBrain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco CA 94143 USABrain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco CA 94143 USABrain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco CA 94143 USAThe Notch signaling cascade is deregulated in diverse cancer types. Specific Notch function in cancer is dependent on the cellular context, the particular homologs expressed, and cross-talk with other signaling pathways. We have previously shown that components of the Notch signaling pathway are deregulated in meningiomas. How-ever, the functional consequence of abnormal Notch signaling to meningiomas is unknown. Here, we report that exogenous expression of the Notch pathway effector, HES1, is associated with tetraploid cells in meningioma cell lines. Activated Notch1 and Notch2 receptors induced endogenous HES1 expression and were associated with tetraploidy in meningiomas. Tetraploid meningioma cells exhibited nuclear features of chromosomal instability and increased frequency of nuclear atypia, such as multipolar mitotic spindles and accumulation of cells with large nuclei. FACS-sorted tetraploid cells are viable but have higher rates of spontaneous apoptosis when compared with diploid cells. We have used spectral karyotyping to show that, in contrast to diploid cells, tetraploid cells develop a higher number of both numerical and structural chromosomal abnormalities. Our findings identify a novel function for the Notch signaling pathway in generating tetraploidy and contributing to chromosomal instability. We speculate that abnormal Notch signaling pathway is an initiating genetic mechanism for meningioma and potentially promotes tumor development.http://www.sciencedirect.com/science/article/pii/S1476558608801492 |
| spellingShingle | Gilson S. Baia Stefano Stifani Edna T. Kimura Michael W. McDermott Russell O. Pieper Anita Lal Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas Neoplasia: An International Journal for Oncology Research |
| title | Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas |
| title_full | Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas |
| title_fullStr | Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas |
| title_full_unstemmed | Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas |
| title_short | Notch Activation Is Associated with Tetraploidy and Enhanced Chromosomal Instability in Meningiomas |
| title_sort | notch activation is associated with tetraploidy and enhanced chromosomal instability in meningiomas |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608801492 |
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