Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Xiao Hong LiuWen Jie Zhang

Abstract

Interleukin-4 (IL-4)-induced Stat6 activities (phenotypes) vary among human cancer cells, of which the HT-29 cell line carries an active Stat6(high) phenotype, while Caco-2 carries a defective Stat6(null) phenotype, respectively. Cancer cells with Stat6(high) show resistance to apoptosis and exaggerated metastasis, suggesting the clinical significance of Stat6 phenotypes. We previously showed that Stat6(high) HT-29 cells exhibited low constitutive expression of Stat6-negative regulators SOCS-1 and SHP-1 because of gene hypermethylation. This study further examined the constitutive expression of other closely related SOCS family numbers including SOCS-3, SOCS-5, SOCS-7, and CISH using RT-PCR. Similar to SOCS-1 and SHP-1, Stat6(high) HT-29 cells expressed low constitutive mRNA of SOCS-3, SOCS-7, and CISH than Stat6(null) Caco-2 cells. Interestingly, DNA demethylation using 5-aza-2'-deoxycytidine in HT-29 cells up-regulated mRNA expression of the above genes, indicating a hypermethylation status, which was confirmed by methylation-specific sequencing in selected SOCS-3 gene. Furthermore, defective Stat6(null) Caco-2 exhibited impaired phosphorylation of Stat6 after IL-4 stimulation by flow cytometry, in keeping with the notion of ...Continue Reading

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Citations

Nov 15, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sungpil YoonSuk Woo Nam
Oct 11, 2012·Genetic Testing and Molecular Biomarkers·Mehri IgciA Tuncay Demiryurek
Apr 24, 2014·Molecular Biology International·Walid SasiKefah Mokbel

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Methods Mentioned

BETA
flow cytometry
PCR
PCRs
electrophoretic mobility shift assay

Software Mentioned

SPSS

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