Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.

ABSTRACT:

Purpose

PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer.

Experimental design

We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and array CGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort of ovarian cancer patients.

Results

Con

SUBMITTER: Konecny GE 

PROVIDER: S-EPMC4598646 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature