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

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• 14-3-3Sigma acts as a tumor suppressor, regulating cell cycle and apoptosis.
• Loss of 14-3-3Sigma expression is observed in various cancers, with promoter hypermethylation as a proposed silencing mechanism.
• Prostate adenocarcinoma and precursor lesions show reduced 14-3-3Sigma expression.

Purpose of the Study:

• To investigate the frequency and extent of 14-3-3Sigma promoter methylation in benign and cancerous prostate tissues.
• To correlate methylation levels with clinical and pathological parameters.
• To assess 14-3-3Sigma mRNA expression in prostate cancer cell lines.

Main Methods:

• Quantitative methylation-specific PCR (QMSP) was used to analyze promoter methylation in 121 prostate carcinoma (PCa) tissues, 39 high-grade prostatic intraepithelial neoplasias (HGPIN), 29 benign prostate hyperplasia (BPH) tissues, and 4 prostate cancer cell lines.
• The percentage of methylated alleles (PMA) was calculated.
• RT-PCR was performed on cell lines to measure 14-3-3Sigma mRNA expression.

Main Results:

• Ubiquitous 14-3-3Sigma promoter methylation was detected in PCa, HGPIN, BPH, and cancer cell lines.
• The PMA in HGPIN was significantly lower than in PCa or BPH (P < 0.0001).
• No significant difference in PMA was observed between PCa and BPH.
• PMA did not correlate with any clinicopathological parameters.
• All tested prostate cancer cell lines expressed 14-3-3Sigma mRNA.

Conclusions:

• 14-3-3Sigma promoter methylation is a frequent epigenetic event in prostate tissues and cell lines.
• Progressive accumulation of methylated 14-3-3Sigma alleles from HGPIN to PCa suggests a role in prostate carcinogenesis.
• Mechanisms beyond promoter methylation may be involved in 14-3-3Sigma downregulation.