Knockout of Brca1-interacting factor Ola1 in female mice induces tumors with estrogen suppressible centrosome amplification.
Biochim Biophys Acta Mol Basis Dis
; 1870(5): 167138, 2024 06.
Article
de En
| MEDLINE
| ID: mdl-38537683
ABSTRACT
Obg-like ATPase 1 (OLA1) is a binding protein of Breast cancer gene 1 (BRCA1), germline pathogenic variants of which cause hereditary breast cancer. Cancer-associated variants of BRCA1 and OLA1 are deficient in the regulation of centrosome number. Although OLA1 might function as a tumor suppressor, the relevance of OLA1 deficiency to carcinogenesis is unclear. Here, we generated Ola1 knockout mice. Aged female Ola1+/- mice developed lymphoproliferative diseases, including malignant lymphoma. The lymphoma tissues had low expression of Ola1 and an increase in the number of cells with centrosome amplification. Interestingly, the proportion of cells with centrosome amplification in normal spleen from Ola1+/- mice was higher in male mice than in female mice. In human cells, estrogen stimulation attenuated centrosome amplification induced by OLA1 knockdown. Previous reports indicate that prominent centrosome amplification causes cell death but does not promote tumorigenesis. Thus, in the current study, the mild centrosome amplification observed under estrogen stimulation in Ola1+/- female mice is likely more tumorigenic than the prominent centrosome amplification observed in Ola1+/- male mice. Our findings provide a possible sex-dependent mechanism of the tumor suppressor function of OLA1.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Souris knockout
/
Centrosome
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Protéine BRCA1
/
Oestrogènes
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
/
Biochim. biophys. acta, Mol. basis dis
/
Biochimica et biophysica acta. Molecular basis of disease
Année:
2024
Type de document:
Article
Pays de publication:
Pays-Bas