p27(kip1): A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers

Ricardo V. Lloyd, Lori A. Erickson, Long Jin, Elzbieta Kulig, Xiang Qian, John C. Cheville, Bernd W. Scheithauer

Research output: Contribution to journalReview articlepeer-review

523 Scopus citations

Abstract

p27(kip1) (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-β. Since the cloning of the p27 gene in 1994, a host of other functions have 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 resistance in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mainly at the post-translational level with protein degradation by the ubiquitin-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 the regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalAmerican Journal of Pathology
Volume154
Issue number2
DOIs
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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