BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors.

ABSTRACT: Heterozygous germline mutations in BRCA2 predispose to breast and ovarian cancer. Contrary to non-cancerous cells, where BRCA2 deletion causes cell cycle arrest or cell death, tumors carrying BRCA2 inactivation continue to proliferate. Here we set out to investigate adaptation to loss of BRCA2 focusing on genome-wide transcriptome alterations. Human cells in which BRCA2 expression is inhibited for 4 or 28 days are subjected to RNA-seq analyses revealing a biphasic response to BRCA2 abrogation. The early, acute response consists of downregulation of genes involved in cell cycle progression, DNA replication and repair and is associated with cell cycle arrest in G1. Surprisingly, the late, chronic response consists predominantly of upregulation of interferon-stimulated genes (ISGs). Activatio

SUBMITTER: Reislander T 

PROVIDER: S-EPMC6637138 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature