Cyclin D1 and P27KIP1: The Gatekeepers of Dysplasia

There is increasing evidence suggesting that cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CDIs) either are themselves targets for genetic change in cancer or are disrupted secondarily by other oncogenic events. Cyclin D1 and p27KIP1 are two important regulators at the G1/S checkpoint. Cyclin D1 is an oncogene of cell cycle regulation with positive effect. Normally, cyclin D1 at G1 is constant or at a very low level and its excessive expression may be associated with the disordered proliferation of cells leading to malignant change. On the other hand, p27KIP1 is an anti-oncogene for cell cycle regulation, which functions as a negative regulator. Under the regulation of TGF-β, p27KIP1 inhibits the activity of oncogenes and controls the transition of the G1/S phase mainly by the interaction with CDK and CDK-Cyclin in order to inhibit cell proliferation and give cells opportunities to repair DNA. In addition, p27KIP1 not only acts as CDK inhibitor, but also promotes cell differentiation and induces the apoptosis of cells. In this article we review studies that have explored the effects of cyclin D1 and P27KIP1 on cancer progression and dysplasia with a specific focus on oral dysplasia and oral squamous cell carcinoma (OSCC). We also aim to shed some light on the different means of evaluating the interaction between Cyclin D1 and P27KIP1 as well as the immunohistochemical reactions associated with different forms of cyclin D1.