Role of cyclin-dependent kinase inhibitors in pituitary tumorigenesis : an update

Human pituitary adenomas are common and potentially serious neoplasms that account for 10- 15% of all intracranial neoplasms. In spite of extensive investigations, the molecular basis of human pituitary tumorigenesis remains elusive. The cell cycle is driven by protein complexes composed of cyclins and cyclin-dependent kinases（CDKs）. CDK inhibitors（CKIs）serve as negative regulators of cell cycle. CKIs include two distinct families : the INK4 family comprising p16INK4A, p15INK4B, p18INK4C, and p19INK4D and the Cip/Kip family including p21CIP1, p27KIP1, and p57KIP2. Dysregulation in CKIs are recognized as critical factors in tumorigenesis. In recent years, extensive studies have demonstrated that mutations, underexpression, and DNA methylation of the CKIs genes were frequently observed in various types of human cancers. However, the role of CKIs in human pituitary tumors has been elucidated to a limited extent. Here we review the potential role of CKIs in human pituitary adenomas concentrating on gene mutations, promoter methylation, and mRNA or protein expression levels.