Cyclin D mediates tolerance of genome-doubling in cancers with functional p53.

ABSTRACT:

Background

Aneuploidy and chromosomal instability (CIN) are common features of human malignancy that fuel genetic heterogeneity. Although tolerance to tetraploidization, an intermediate state that further exacerbates CIN, is frequently mediated by TP53 dysfunction, we find that some genome-doubled tumours retain wild-type TP53. We sought to understand how tetraploid cells with a functional p53/p21-axis tolerate genome-doubling events.

Methods

We performed quantitative proteomics in a diploid/tetraploid pair within a system of multiple independently derived TP53 wild-type tetraploid clones arising spontaneously from a diploid progenitor. We characterized adapted and acute tetraploidization in a variety of flow cytometry and biochemical assays and tested our findings against h

SUBMITTER: Crockford A 

PROVIDER: S-EPMC5391719 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature