Respective roles of Pik3ca mutations and cyproterone acetate impregnation in mouse meningioma tumorigenesis.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
28
01
2023
accepted:
28
04
2023
revised:
05
04
2023
medline:
16
8
2023
pubmed:
16
5
2023
entrez:
15
5
2023
Statut:
ppublish
Résumé
Despite their rarity, PIK3CA mutations in meningiomas have raised interest as potentially targetable, ubiquitous mutations owing to their presence in sporadic benign and malignant tumors but also in hormone-related cases. Using new genetically engineered mouse models, we here demonstrate that Pik3ca mutations in postnatal meningeal cells are sufficient to promote meningioma formation but also tumor progression in mice. Conversely, hormone impregnation, whether alone or in association with Pik3ca and Nf2 mutations, fails to induce meningioma tumorigenesis while promoting breast tumor formation. We then confirm in vitro the effect of Pik3ca mutations but not hormone impregnation on the proliferation of primary cultures of mouse meningeal cells. Finally, we show by exome analysis of breast tumors and meninges that hormone impregnation promotes breast tumor formation without additional somatic oncogenic mutation but is associated with an increased mutational burden on Pik3ca-mutant background. Taken together, these results tend to suggest a prominent role of Pik3ca mutations over hormone impregnation in meningioma tumorigenesis, the exact effect of the latter is still to be discovered.
Identifiants
pubmed: 37188724
doi: 10.1038/s41417-023-00621-2
pii: 10.1038/s41417-023-00621-2
doi:
Substances chimiques
Cyproterone Acetate
4KM2BN5JHF
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1114-1123Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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