title: DNA methylation regulates constitutive expression of Stat6 regulatory genes SOCS-1 and SHP-1 in colon cancer cells.
abstract: OBJECTIVE
  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 Stat6(null) Caco-2 cells, Stat6(high) 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.
authors: Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, 832002 Shehezi, Xinjiang, China.
authors: Shuang Bing
authors: SB
authors: Xu
authors: Xiao Hong
authors: XH
authors: Liu
authors: Ben Hui
authors: BH
authors: Li
authors: Yan
authors: Y
authors: Zhang
authors: Jia
authors: J
authors: Yuan
authors: Qin
authors: Q
authors: Yuan
authors: Pin Dong
authors: PD
authors: Li
authors: Xian Zi
authors: XZ
authors: Yang
authors: Feng
authors: F
authors: Li
authors: Wen Jie
authors: WJ
authors: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; C508598:IL4 protein, human; C108944:SOCS1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4; D000077209:Decitabine; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D001374:Azacitidine