Rv. Lloyd et al., P27(kip1): A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers, AM J PATH, 154(2), 1999, pp. 313-323
Citations number
120
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
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.