SLIT2 is epigenetically silenced in ovarian cancers and suppresses growth when activated

Asian Pac J Cancer Prev. 2011;12(3):791-5.

Abstract

Objectives: The SLIT2 gene is a novel tumor suppressor gene, whose hypermethylation has been detected in several malignances, including breast cancer, colorectal carcinoma and gliomas. In this study, we assessed the status of SLIT2 and its functions in ovarian cancers and cell lines.

Methods: Methylation-specific PCR was used to investigate the methylated promoter of SLIT2; the functions of SLIT2 in ovarian cancer cells were measured by MTT, colony formation assay and flow cytometry.

Results: SLIT2 promoter hypermethylation was detected in 56 of 66 (84.8%) ovarian cancer samples and downregulation of SLIT2 expression in 52 (78.8%). The decreased expression was significantly correlated with SLIT2 promoter hypermethylation (p<0.01). Moreover, reversed expression of SLIT2 suppressed cell growth, migration, colony formation abilities and induced more apoptosis.

Conclusions: These results suggest that SLIT2 is a tumor suppressor in ovarian cancer, and may be a novel target for ovarian cancer treatment.

Publication types

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

MeSH terms

  • Apoptosis*
  • Azacitidine / pharmacology
  • Case-Control Studies
  • Cell Proliferation
  • DNA / genetics
  • DNA Methylation*
  • Epigenomics*
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Genes, Tumor Suppressor
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • DNA
  • Azacitidine
  • Slit homolog 2 protein