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Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer

Oncogene volume 24, pages 6667–6675 (2005)Cite this article

Abstract

A critical region of loss of heterozygosity on human chromosome 13q14 harbors the tumor suppressor gene DICE1 (DDX26). To elucidate the reduced DICE1 expression in tumor cells, the putative promoter sequence upstream of the DICE1 gene was analysed. This sequence shows a high GC content and is rich in CpG sites and binding sites of transcriptional factors. Promoter activity was identified within three overlapping fragments of the 800 bp sequence upstream of the DICE1 gene. A 13 bp deletion polymorphism detected in the DICE1 promoter region showed a decreased activity compared with the undeleted variant. However, this 13 bp deletion was seen in male control samples and patients with prostate cancer or benign prostatic hyperplasia at similar rates. A reduced DICE1 expression was observed in prostate cancer cell lines DU145 and LNCaP. This downregulation is associated with hypermethylation of the DICE1 promoter. Treatment of both prostate cancer cell lines with 5-azacytidine leads to upregulation of DICE1 expression. Hypermethylation of CpG sites of the DICE1 promoter was observed in four of eight analysed prostate cancers. This study suggests that transcriptional repression of DICE1 is caused by hypermethylation of the DICE1 promoter region in prostate cancer cells.

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Acknowledgements

We thank Ms S Engelberg and Mr I Gläser for helpful technical assistance. This work was supported in part by the Dr-Mildred-Scheel Foundation.

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Authors and Affiliations

  1. Institute of Human Genetics, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, Magdeburg, 39120, Germany

    Albrecht Röpke, Ilse Wieland & Peter F Wieacker

  2. Institute of Pathology, Otto-von-Guericke-University Magdeburg, Magdeburg, 39120, Germany

    Peter Buhtz

  3. Department of Urology, Otto-von-Guericke-University Magdeburg, Magdeburg, 39120, Germany

    Malte Böhm, Jeannette Seger & Ernst P Allhoff

Authors
  1. Albrecht Röpke
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  2. Peter Buhtz
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  3. Malte Böhm
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  4. Jeannette Seger
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  5. Ilse Wieland
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Correspondence to Peter F Wieacker.

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Röpke, A., Buhtz, P., Böhm, M. et al. Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer. Oncogene 24, 6667–6675 (2005). https://doi.org/10.1038/sj.onc.1208824

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  • DOI: https://doi.org/10.1038/sj.onc.1208824

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