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DNA methylation regulates constitutive expression of Stat6 regulatory genes SOCS-1 and SHP-1 in colon cancer cells
Journal of Cancer Research & Clinical Oncology, 06/30/09
Xu SB et al. - In a study to investigate possible mechanism(s) involved in formation of varying Stat6 activities/phenotypes, these findings suggest that DNA methylation controls the constitutive expression of negative Stat6 regulatory genes, which may affect Stat6 activities.
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 expression of SOCS-1 and SHP-1 after demethylation using 5-aza-2?-deoxycytidine.
- 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.
- Demethylation in HT-29 cells recovered the constitutive expression of SOCS-1 and SHP-1.
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