| Online-Ressource |
Verfasst von: | Moussa, Amira-Talaat [VerfasserIn]  |
| Cosenza, Marco R. [VerfasserIn]  |
| Wohlfromm, Timothy [VerfasserIn]  |
| Brobeil, Katharina [VerfasserIn]  |
| Hill, Anthony [VerfasserIn]  |
| Patrizi, Annarita [VerfasserIn]  |
| Müller-Decker, Karin [VerfasserIn]  |
| Holland-Letz, Tim [VerfasserIn]  |
| Jauch, Anna [VerfasserIn]  |
| Kraft, Bianca [VerfasserIn]  |
| Krämer, Alwin [VerfasserIn]  |
Titel: | STIL overexpression shortens lifespan and reduces tumor formation in mice |
Verf.angabe: | Amira-Talaat Moussa, Marco R. Cosenza, Timothy Wohlfromm, Katharina Brobeil, Anthony Hill, Annarita Patrizi, Karin Müller-Decker, Tim Holland-Letz, Anna Jauch, Bianca Kraft, Alwin Krämer |
E-Jahr: | 2024 |
Jahr: | October 28, 2024 |
Umfang: | 28 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 06.06.2025 |
Titel Quelle: | Enthalten in: Public Library of SciencePLoS Genetics |
Ort Quelle: | San Francisco, Calif. : Public Library of Science, 2005 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 20(2024), 10, Artikel-ID e1011460, Seite 1-28 |
ISSN Quelle: | 1553-7404 |
Abstract: | Centrosomes are the major microtubule organizing centers of animal cells. Supernumerary centrosomes are a common feature of human tumors and associated with karyotype abnormalities and aggressive disease, but whether they are cause or consequence of cancer remains controversial. Here, we analyzed the consequences of centrosome amplification by generating transgenic mice in which centrosome numbers can be increased by overexpression of the structural centrosome protein STIL. We show that STIL overexpression induces centrosome amplification and aneuploidy, leading to senescence, apoptosis, and impaired proliferation in mouse embryonic fibroblasts, and microcephaly with increased perinatal lethality and shortened lifespan in mice. Importantly, both overall tumor formation in mice with constitutive, global STIL overexpression and chemical skin carcinogenesis in animals with inducible, skin-specific STIL overexpression were reduced, an effect that was not rescued by concomitant interference with p53 function. These results suggest that supernumerary centrosomes impair proliferation in vitro as well as in vivo, resulting in reduced lifespan and delayed spontaneous as well as carcinogen-induced tumor formation. |
DOI: | doi:10.1371/journal.pgen.1011460 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1371/journal.pgen.1011460 |
| DOI: https://doi.org/10.1371/journal.pgen.1011460 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Aneuploidy |
| Animals |
| Apoptosis |
| Carcinogenesis |
| Cell Proliferation |
| Centrosome |
| Fibroblasts |
| Humans |
| Longevity |
| Mice |
| Mice, Transgenic |
| Neoplasms |
| Skin Neoplasms |
| T-Cell Acute Lymphocytic Leukemia Protein 1 |
| Tumor Suppressor Protein p53 |
K10plus-PPN: | 1927799163 |
Verknüpfungen: | → Zeitschrift |
STIL overexpression shortens lifespan and reduces tumor formation in mice / Moussa, Amira-Talaat [VerfasserIn]; October 28, 2024 (Online-Ressource)