Cyclin E2 Promotes Whole Genome Doubling in Breast Cancer.

ABSTRACT: Genome doubling is an underlying cause of cancer cell aneuploidy and genomic instability, but few drivers have been identified for this process. Due to their physiological roles in the genome reduplication of normal cells, we hypothesised that the oncogenes cyclins E1 and E2 may be drivers of genome doubling in cancer. We show that both cyclin E1 (CCNE1) and cyclin E2 (CCNE2) mRNA are significantly associated with high genome ploidy in breast cancers. By live cell imaging and flow cytometry, we show that cyclin E2 overexpression promotes aberrant mitosis without causing mitotic slippage, and it increases ploidy with negative feedback on the replication licensing protein, Cdt1. We demonstrate that cyclin E2 localises with core preRC (pre-replication complex) proteins (MCM2, MCM7) on the chr

SUBMITTER: Lee C 

PROVIDER: S-EPMC7463708 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature