Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma

ABSTRACT: Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine astrocytes, as well as patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we furthe

SUBMITTER: Broestl L 

PROVIDER: S-EPMC9345919 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature