Frequent 14-3-3σ promoter methylation in benign and malignant prostate lesions

Rui Henrique, Carmen Jerónimo, Mohammad O. Hoque, André L. Carvalho, Jorge Oliveira, Manuel R. Teixeira, Carlos Lopes, David Sidransky

Research output: Contribution to journalArticle

Abstract

14-3-3σ is a putative tumor suppressor gene involved in cell cycle regulation and apoptosis following DNA damage. 14-3-3σ loss of expression has been reported is several human cancers, including prostate adenocarcinoma and precursor lesions, and promoter hypermethylation has been proposed as the mechanism underlying gene silencing. Here, we investigate the frequency and extent of 14-3-3σ promoter methylation in benign and cancerous prostate tissues. We examined tumor tissue from 121 patients with prostate carcinoma (PCa), 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostate hyperplasia (BPH), as well as four prostate cancer cell lines using quantitative methylation-specific PCR (QMSP). The percentage of methylated alleles (PMA) was calculated and correlated with clinical and pathological parameters. RT-PCR was performed in the cell lines to assess 14-3-3σ mRNA expression. PCa, HGPIN, BPH, and cancer cell lines showed ubiquitous 14-3-3σ promoter methylation. However, the PMA of HGPIN was significantly lower than that of PCa or BPH (P < 0.0001), while PCa and BPH did not significantly differ. The PMA did not correlate with any clinicopathological parameter. All prostate cancer cell lines expressed 14-3-3σ mRNA. 14-3-3σ promoter methylation is a frequent event in prostate tissues and cancer cell lines. Furthermore, there is a progressive accumulation of neoplastic cells with 14-3-3σ methylated alleles from HGPIN to PCa, suggesting a role for this epigenetic event in prostate carcinogenesis. However, other mechanisms besides promoter methylation might be required for effective 14-3-3σ downregulation.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalDNA and Cell Biology
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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