Cyclin dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene.
It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.
A study was conducted to evaluate the levels of Cdk2, cyclin E, p21 and p27 in growth hormone adenomas (GHPAs) and analyze their association with clinicopathologic features in 46 patients with GHPAs. Accordingly, we found that the levels of cyclin E and Cdk2 were much higher in invasive GHPA specimens than those in non-invasive specimens (p<0.05). Lower p21 and p27 levels were detected through tissue micro-assay (TMA). Significant differences were found between cyclin E expression and tumor size (p=0.039), cyclin E expression and invasion (p=0.003), and p21 expression and tumor size (p=0.039). Furthermore, tumors were more likely to require whole resection in patients with low cyclin E levels (12/23 vs 19/23, p=0.028). The average progression free survival (PFS) time in the high p27 group was longer than that in the low p27 group (p=0.006). RT-PCR and western-blot analysis revealed a similar trend for Cdk2, cyclin E, p21 and p27 protein levels in GH specimens (p<0.01 for all). An average of 33 CpG sites per sample were analyzed using MALDI-TOF mass array, and in 7 out of the 33 CpG sites, methylation levels of p27 were more than 50%. There were significant differences in 4 CpG sites between invasive and non-invasive specimens (p<0.01). Considering the well-documented role of Cdk2, cyclin E and p27 in cell cycle regulation, overexpression of cyclin E/Cdk2 and loss of p27 appears to be associated with poor prognosis and may play a role in treatment of GHPAs in the future 1).