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Epigenetic inactivation of the SFRP1 gene in esophageal squamous cell carcinoma

Ying Meng1, Qing-Gang Wang, Jun-Xiong Wang

  • 1Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050 Beijing, China.

Digestive Diseases and Sciences
|May 14, 2011
PubMed
Abstract

Insights

Secreted frizzled-related protein 1 (SFRP1) gene promoter hypermethylation frequently inactivates SFRP1 in esophageal squamous cell carcinoma (ESCC). Epigenetic modifications, including DNA methylation and histone acetylation, cooperatively regulate SFRP1 expression in ESCC.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Secreted frizzled-related protein 1 (SFRP1) acts as a Wnt signaling modulator.
  • SFRP1 inactivation via promoter methylation is common in various cancers.
  • The role of SFRP1 in esophageal squamous cell carcinoma (ESCC) remains unclear.

Purpose of the Study:

  • To investigate the epigenetic inactivation of the SFRP1 gene in ESCC.
  • To determine the correlation between SFRP1 promoter methylation and its expression in ESCC.
  • To explore the role of histone modifications in SFRP1 regulation in ESCC.

Main Methods:

  • Analysis of SFRP1 promoter methylation using methylation-specific PCR and bisulfite sequencing.
  • Assessment of SFRP1 gene expression via reverse-transcription PCR and immunohistochemistry.
  • Investigation of histone modifications at the SFRP1 promoter using chromatin immunoprecipitation assays.

Main Results:

  • SFRP1 promoter hypermethylation was observed in 95% of ESCC tissues and all ESCC cell lines.
  • SFRP1 promoter methylation strongly correlated with reduced SFRP1 gene expression.
  • Combined treatment with DAC and TSA restored SFRP1 mRNA expression, indicating a role for DNA methylation and histone acetylation.

Conclusions:

  • Promoter hypermethylation of SFRP1 is a frequent epigenetic event in ESCC.
  • DNA methylation and histone acetylation cooperatively regulate SFRP1 gene expression in ESCC.
  • SFRP1 may serve as a potential epigenetic target for ESCC therapy.

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