Journal of Cancer Research and Clinical Oncology

, Volume 135, Issue 12, pp 1791–1798

DNA methylation regulates constitutive expression of Stat6 regulatory genes SOCS-1 and SHP-1 in colon cancer cells

  • Shuang Bing Xu
  • Xiao Hong Liu
  • Ben Hui Li
  • Yan Zhang
  • Jia Yuan
  • Qin Yuan
  • Pin Dong Li
  • Xian Zi Yang
  • Feng Li
  • Wen Jie Zhang
Original Paper

DOI: 10.1007/s00432-009-0627-z

Cite this article as:
Xu, S.B., Liu, X.H., Li, B.H. et al. J Cancer Res Clin Oncol (2009) 135: 1791. doi:10.1007/s00432-009-0627-z

Abstract

Purpose

Stat6 signaling is active in cancer cells and IL-4-induced Stat6 activities or Stat6 activational phenotypes vary among cancer cells. This study aimed at investigating possible mechanism(s) involved in the formation of varying Stat6 activities/phenotypes.

Methods

Stat6 regulatory genes, SOCS-1 and SHP-1, were examined for mRNA expression using RT-PCR, and their promoter DNA methylation was assayed by methylation-specific PCR in Stat6-phenotyped colon cancer cell lines. DNA methylation was then verified by sequencing. RT-PCR assay and Western blotting were used to detect the expression of SOCS-1 and SHP-1 after demethylation using 5-aza-2′-deoxycytidine.

Results

Compared with Stat6null Caco-2 cells, Stat6high HT-29 cells showed decreased constitutive expression of SOCS-1 and SHP-1, which correlated with DNA hypermethylation in these genes’ promoters. Interestingly, demethylation in HT-29 cells recovered the constitutive expression of SOCS-1 and SHP-1.

Conclusions

These findings suggest that DNA methylation controls the constitutive expression of negative Stat6 regulatory genes, which may affect Stat6 activities.

Keywords

Colon cancer DNA methylation IL-4 SOCS-1 SHP-1 Stat6 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Shuang Bing Xu
    • 1
    • 2
    • 3
    • 4
  • Xiao Hong Liu
    • 1
    • 3
    • 5
  • Ben Hui Li
    • 1
    • 3
  • Yan Zhang
    • 1
  • Jia Yuan
    • 5
  • Qin Yuan
    • 1
  • Pin Dong Li
    • 1
  • Xian Zi Yang
    • 4
  • Feng Li
    • 1
  • Wen Jie Zhang
    • 1
    • 2
    • 3
  1. 1.Laboratory of Xinjiang Endemic and Ethnic DiseasesShihezi University School of MedicineSheheziChina
  2. 2.Department of Immunology, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Medical OncologyZhongnan Hospital and Cancer Research Center, Wuhan UniversityWuhanChina
  4. 4.Department of Medical Oncology, Yunyang Medical CollegeTaihe HospitalShiyanChina
  5. 5.Department of Medical OncologyXiangfan Central HospitalXiangfanChina