Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints.

ABSTRACT: The cell has many mechanisms for protecting the integrity of its genome. These mechanisms are often weakened or absent in many cancers, leading to high rates of chromosomal instability in tumors. Control of the cell cycle is crucial for the function of these checkpoints, and is frequently lost in cancers as well. Overexpression of Cyclin D1 in a large number of breast cancers causes overactivation of the cyclin-dependent kinases, including Cdk2. Constitutive Cdk2 activation through Cyclin D1 generates tumors in mice that are aneuploid and have many characteristics indicative of chromosomal instability. Expression of these complexes in the MCF10A cell line leads to retinoblastoma protein (Rb) hyperphosphorylation, a subsequent increase in proliferation rate, and increased expression of the

SUBMITTER: Jahn SC 

PROVIDER: S-EPMC3635462 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature