Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice.
Dis Model Mech
; 17(5)2024 May 01.
Article
em En
| MEDLINE
| ID: mdl-38616733
ABSTRACT
Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin-mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to those in Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mouse bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
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Proteínas Proto-Oncogênicas c-myc
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Caspases
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Quinases Associadas a rho
Limite:
Animals
Idioma:
En
Revista:
Dis Model Mech
Assunto da revista:
MEDICINA
Ano de publicação:
2024
Tipo de documento:
Article