Digestive Diseases and Sciences

, Volume 56, Issue 11, pp 3195–3203

Epigenetic Inactivation of the SFRP1 Gene in Esophageal Squamous Cell Carcinoma

  • Ying Meng
  • Qing-Gang Wang
  • Jun-Xiong Wang
  • Sheng-tao Zhu
  • Yue Jiao
  • Peng Li
  • Shu-tian Zhang
Original Article

DOI: 10.1007/s10620-011-1734-7

Cite this article as:
Meng, Y., Wang, QG., Wang, JX. et al. Dig Dis Sci (2011) 56: 3195. doi:10.1007/s10620-011-1734-7

Abstract

Introduction

The secreted frizzled-related protein 1 (SFRP1) gene, as a Wnt signaling modulator, is frequently inactivated by promoter methylation in many tumors including gastric cancer, breast cancer, oral squamous cell carcinoma, and esophageal adenocarcinoma. However, the role of SFRP1 in esophageal squamous cell carcinoma (ESCC) is not clear. In this study, we investigated the epigenetic inactivation of the SFRP1 gene in ESCC.

Methods

Nine ESCC cell lines, two immortalized human esophageal epithelial cell lines, twenty ESCC tissues, and paired adjacent nontumor tissues were analyzed in the study. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, reverse-transcription PCR, immunohistochemistry, and chromatin immunoprecipitation assay were used to detect SFRP1 promoter methylation, expression of the SFRP1 gene, and histone modification in the SFRP1 promoter region.

Results

The SFRP1 promoter was found to be highly methylated in 95% (19/20) of the ESCC tissues and in nine ESCC cell lines, compared with 65% (13/20) of the paired nontumor tissues. Moreover, we confirmed that complete methylation of the SFRP1 gene promoter was correlated with its greatly reduced expression level. After individual treatment with 5-aza-2′-deoxycytidine (DAC) and trichostatin A (TSA), the messenger RNA (mRNA) level of the SFRP1 gene was not obviously rescued in the EC9706 cell line. Combined incubation with DAC and TSA can, however, substantially increase the SFRP1 mRNA expression level in the EC9706 cell line. Chromatin immunoprecipitation assay showed that acetylated histone H3 and H4 were found in the SFRP1 promoter region.

Conclusion

Promoter hypermethylation of SFRP1 is a frequent event in ESCC. Promoter methylation and histone acetylation may cooperatively regulate expression of the SFRP1 gene.

Keywords

Esophageal squamous cell carcinomaDNA methylationSFRP1Acetylation

Supplementary material

10620_2011_1734_MOESM1_ESM.xls (16 kb)
Supplementary material 1 (XLS 16 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ying Meng
    • 1
  • Qing-Gang Wang
    • 1
  • Jun-Xiong Wang
    • 1
  • Sheng-tao Zhu
    • 1
  • Yue Jiao
    • 1
  • Peng Li
    • 1
  • Shu-tian Zhang
    • 1
  1. 1.Department of GastroenterologyBeijing Friendship Hospital Affiliated to the Capital Medical UniversityBeijingChina