p27 deregulation in breast cancer: prognostic significance and implications for therapy

J Mammary Gland Biol Neoplasia. 2004 Jan;9(1):67-80. doi: 10.1023/B:JOMG.0000023589.00994.5e.

Abstract

p27 is a key regulator of G1-to-S phase progression. It prevents premature activation of cyclin E-cdk2 in G1 and promotes the assembly and activation of D-type cyclin-cdks. While the p27 gene is rarely mutated in human cancers, the action of p27 is impaired in breast and other human cancers through accelerated p27 proteolysis, sequestration by cyclin D-cdks, and by p27 mislocalization in tumor cell cytoplasm. Reduced p27 protein is strongly associated with high histopathologic tumor grade, reflecting a lack of tumor differentiation. Loss of p27 is also an indicator of poor patient outcome in a majority of breast cancer studies, including node negative disease. The broad application of p27 in the clinical evaluation of breast cancer prognosis will require a consensus on methods of tumor fixation, staining, and scoring. This review will focus on mechanisms of p27 regulation in normal cells and how deregulation of p27 may arise in breast and other human cancers. The prognostic significance of p27 in human breast cancer and the possible therapeutic implications of these findings will also be reviewed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Cell Adhesion
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle*
  • Cell Transformation, Neoplastic*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Enzyme Inhibitors
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Prognosis
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27