Arsenic trioxide increases expression of secreted frizzled-related protein 1 gene and inhibits the WNT/β-catenin signaling pathway in Jurkat cells

Wang,Yan; Wang,Zunsong; Li,Hong; Xu,Wenwei; Dong,Lin; Guo,Yan; Feng,Saran; Bi,Kehong; Zhu,Chuansheng

doi:10.3892/etm.2017.4184

Arsenic trioxide increases expression of secreted frizzled-related protein 1 gene and inhibits the WNT/β-catenin signaling pathway in Jurkat cells

Authors:
- Yan Wang
- Zunsong Wang
- Hong Li
- Wenwei Xu
- Lin Dong
- Yan Guo
- Saran Feng
- Kehong Bi
- Chuansheng Zhu
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Affiliations: Department of Hematology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China, Department of Nephrology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: March 6, 2017 https://doi.org/10.3892/etm.2017.4184
Pages: 2050-2055

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Abstract

The aim of the present study was to investigate the demethylation effect of arsenic trioxide (As2O3) on the secreted frizzled-related protein 1 (SFRP1) gene and its ability to inhibit the Wingless‑type MMTV integration site family (WNT) pathway in Jurkat cells. Methylation-specific polymerase chain reaction was used to examine the CpG island methylation status of the SFRP1 gene in leukemia cell lines. In addition, the effects on Jurkat cells of treatment with different concentrations of As2O3 for 48 h were investigated. Reverse transcription‑quantitative polymerase chain reaction was employed to measure the expression of mRNAs, while western blot analysis was used to examine protein expression in cells. The SFRP1 gene was methylated in Jurkat cells. However, both methylated and unmethylated SFRP1 genes were detected in HL60 and K562 cells. In normal bone marrow mononuclear cells, the SFRP1 gene was unmethylated. Following treatment with As2O3 for 48 h, the SFRP1 gene was demethylated, and the mRNA and protein expression levels of the SFRP1 gene were increased. By contrast, the mRNA and protein expression levels of β‑catenin and cyclin Dl were downregulated. The protein expression of c‑myc was also downregulated, but As2O3 exhibited no significant effect on the mRNA expression of c‑myc. Abnormal methylation of the SFRP1 gene was detected in Jurkat cells. These results suggest that As2O3 activates SFRP1 gene expression at the mRNA and protein levels in Jurkat cells by demethylation of the SFRP1 gene. Furthermore, they indicate that As2O3 regulates WNT target genes and controls the growth of Jurkat cells through the WNT/β-catenin signaling pathway.

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