Overexpression of PLK1 is associated with poor survival by inhibiting apoptosis via enhancement of survivin level in esophageal squamous cell carcinoma

Int J Cancer. 2009 Feb 1;124(3):578-88. doi: 10.1002/ijc.23990.

Abstract

PLK1 is essential for the maintenance of genomic stability during mitosis. In our study, we found that overexpression of PLK1 was an independent prognostic factor (RR=4.253, p=0.020) and significantly correlated with survivin, an antiapoptotic protein, in esophageal squamous cell carcinoma (ESCC). Reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed upregulation of PLK1 mRNA and amplification of PLK1 gene, respectively. Depletion of PLK1 activated the intrinsic apoptotic pathway, which was substantiated by loss of mitochondrial membrane potential, reduction of Mcl-1 and Bcl-2 as well as activation of caspase-9. Coimmunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin and PLK1 depletion led to downregulation of survivin. Cotransfection of survivin constructs could partially reverse PLK1-depletion-induced apoptosis. These data suggest that PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC. Survivin is probably involved in antiapoptotic function of PLK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins / biosynthesis*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • In Situ Hybridization, Fluorescence
  • Inhibitor of Apoptosis Proteins
  • Kaplan-Meier Estimate
  • Male
  • Membrane Potential, Mitochondrial / physiology
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Protein-Serine-Threonine Kinases / biosynthesis*
  • Proto-Oncogene Proteins / biosynthesis*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Tissue Array Analysis

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Survivin
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1