P27(kip1): A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers

p27(kip1) (p27) is a member of the universal cyclin-dependent kinase inhibi tor (CDKI) family. p27 expression is regulated by cell contact inhibition a nd by specific growth factors, such as transforming growth factor (TGF)-bet a, Since the cloning of the p27 gene in 1994, a host of other functions hav e been associated with this cell cycle protein. In addition to its role as a CDKI, p27 is a putative tumor suppressor gene, regulator of drug resistan ce in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p 27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mai nly at the post-translational level with protein degradation by the ubiquit in-proteasome pathway. A large number of studies have characterized p27 as an independent prognostic factor in various human cancers, including breast , colon, and prostate adenocarcinomas. Here we review the role of p27 in th e regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicatin g the increasingly important roles of p27, other CDKIs, and cyclins in endo crine cell hyperplasia and tumor development.