Prognostic and therapeutic implications of increased ATP citrate lyase expression in human epithelial ovarian cancer

Oncol Rep. 2012 Apr;27(4):1156-62. doi: 10.3892/or.2012.1638. Epub 2012 Jan 16.

Abstract

Altered metabolism is one of the most significant features of cancer cells. ATP citrate lyase (ACL), a key enzyme in de novo lipid synthesis, has been reported to be overexpressed or activated in several cancer types. To determine the role of ACL in ovarian cancer progression, we detected ACL expression in human epithelial ovarian cancer tissues. qRT-PCR and western blotting showed higher ACL expression in malignant tissues compared to normal ovarian tissues. Immunohistochemical analysis showed that phosphorylated ACL was increased in ovarian cancer tissues and that its expression correlated well with tumor grade, FIGO stage and poorer prognosis. To explore the therapeutic potential of ACL, we assessed the effect of ACL-siRNA on cellular proliferation and cell cycle distribution. ACL knockdown inhibited cellular proliferation and induced cell cycle arrest in A2780 cells. Taken together, our findings suggest that ACL may contribute to the pathogenesis of human epithelial ovarian cancer, and may serve as a novel therapeutic target.

MeSH terms

  • ATP Citrate (pro-S)-Lyase / genetics
  • ATP Citrate (pro-S)-Lyase / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Ovarian Epithelial
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • China
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / enzymology*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / therapy
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy
  • Phosphorylation
  • Proportional Hazards Models
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transfection
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • ATP Citrate (pro-S)-Lyase