Deregulation of the cell cycle in cancer

C. Sandhu, J. Slingerland

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Mitogenic and growth-inhibitory signals influence cell-cycle progression through their action on a family of cyclin-dependent kinases (cdks). The activity of cdk complexes is regulated in part by the association of a cyclin partner that acts as a positive effector and by two families of cdk inhibitors, the kinase inhibitor proteins (KIP) and the inhibitors of cdk4 (INK4), which act as negative effectors. In human malignancies, increased expression of cyclins is frequently observed. Cyclin D1 and E are frequently overexpressed in breast cancers, and cyclin E overexpression has been correlated with a poor prognostic outcome. The abrogated expression or the acquisition of mutations that render cdk inhibitors functionally inactive have similarly been found in human malignancies. The p16 gene is frequently deleted or mutated in cancers. Although normal epithelial cells express high levels of p27 protein, reduced levels of p27 have been observed in several human cancers, and this has been consistently correlated with a poor prognostic outcome. In this review, we will provide a brief overview of the cell cycle regulators and then discuss their deregulation in cancers.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalCancer Detection and Prevention
Volume24
Issue number2
StatePublished - Jul 15 2000
Externally publishedYes

Keywords

  • Cancer
  • CDK inhibitors
  • Cell cycle

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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