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Aberrant methylation of the vascular endothelial growth factor receptor-1 gene in prostate cancer

Yasushi Yamada1, Masatoshi Watanabe, Mikio Yamanaka

  • 1Second Department of Pathology, Mie University Faculty of Medicine, Tsu 514-8507, Japan.

Cancer Science
|June 26, 2003
PubMed

Insights

DNA methylation silences cancer genes. In prostate cancer, VEGFR-1 gene re-expression was observed after drug treatment, indicating methylation

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • DNA methylation is a key epigenetic mechanism involved in transcriptional gene silencing.
  • Aberrant DNA methylation patterns are frequently observed in various cancers, including prostate cancer.
  • Understanding methylation's role in prostate cancer is crucial for identifying novel therapeutic targets.

Purpose of the Study:

  • To identify genes regulated by DNA methylation in prostate cancer.
  • To investigate the role of vascular endothelial growth factor receptor 1 (VEGFR-1) methylation in prostate cancer development.

Main Methods:

  • Utilized cDNA microarray analysis to assess gene expression changes in prostate cancer cell lines (LNCaP and DU145) treated with epigenetic drugs.
  • Employed bisulfite sequencing and Combined Bisulfite Restriction Analysis (COBRA) to detect DNA methylation status.
  • Analyzed methylation in both cell lines and primary prostate cancer samples.

Main Results:

  • Drug treatments induced significant gene expression changes (3.4-5.7%) in prostate cancer cell lines.
  • Vascular endothelial growth factor receptor 1 (VEGFR-1) was re-expressed following treatment, with its promoter and exon 1 found to be hypermethylated.
  • VEGFR-1 promoter methylation was detected in 38.1% of primary prostate cancer samples but not in benign samples.

Conclusions:

  • DNA methylation is associated with the loss of VEGFR-1 mRNA expression in prostate cancer.
  • VEGFR-1 methylation is implicated in prostatic carcinogenesis, suggesting its potential as a biomarker or therapeutic target.

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