The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms

BMC Cancer
Tanja HaagReinhard H Dammann

Abstract

Dual specificity phosphatases are a class of tumor-associated proteins involved in the negative regulation of the MAP kinase pathway. Downregulation of the dual specificity phosphatase 2 (DUSP2) has been reported in cancer. Epigenetic silencing of tumor suppressor genes by abnormal promoter methylation is a frequent mechanism in oncogenesis. It has been shown that the epigenetic factor CTCF is involved in the regulation of tumor suppressor genes. We analyzed the promoter hypermethylation of DUSP2 in human cancer, including primary Merkel cell carcinoma by bisulfite restriction analysis and pyrosequencing. Moreover we analyzed the impact of a DNA methyltransferase inhibitor (5-Aza-dC) and CTCF on the epigenetic regulation of DUSP2 by qRT-PCR, promoter assay, chromatin immuno-precipitation and methylation analysis. Here we report a significant tumor-specific hypermethylation of DUSP2 in primary Merkel cell carcinoma (p = 0.05). An increase in methylation of DUSP2 was also found in 17 out of 24 (71%) cancer cell lines, including skin and lung cancer. Treatment of cancer cells with 5-Aza-dC induced DUSP2 expression by its promoter demethylation, Additionally we observed that CTCF induces DUSP2 expression in cell lines that exhibit ...Continue Reading

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Citations

Dec 14, 2019·Anti-cancer Agents in Medicinal Chemistry·Zhiqin LiuDu-Qiang Luo
Oct 6, 2018·Nature Reviews. Clinical Oncology·Paul W HarmsUNKNOWN International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group
Apr 14, 2017·Journal of Cancer Research and Clinical Oncology·Giuseppina ImprotaJürgen C Becker
Jun 22, 2017·Scientific Reports·Steffen KiehlReinhard H Dammann
Aug 8, 2021·International Journal of Molecular Sciences·Valeria PietropaoloUgo Moens
Sep 3, 2021·The Journal of Investigative Dermatology·Paul W HarmsArul M Chinnaiyan

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Methods Mentioned

BETA
PCR
transfection
Assay
immunoprecipitation
ChIP
DNA-immunoprecipitation
PARylation

Software Mentioned

COBRA
GraphPad Quick Calcs
Excel
ChipSeq Encode
UCSC genome browser

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