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  • Oncogenomics
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ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2

Oncogene volume 23, pages 9295–9302 (2004)Cite this article

Abstract

We have identified a gene, ST18 (suppression of tumorigenicity 18, breast carcinoma, zinc-finger protein), within a frequent imbalanced region of chromosome 8q11 as a breast cancer tumor suppressor gene. The ST18 gene encodes a zinc-finger DNA-binding protein with six fingers of the C2HC type (configuration Cys-X5-Cys-X12-His-X4-Cys) and an SMC domain. ST18 has the potential to act as transcriptional regulator. ST18 is expressed in a number of normal tissues including mammary epithelial cells although the level of expression is quite low. In breast cancer cell lines and the majority of primary breast tumors, ST18 mRNA is significantly downregulated. A 160 bp region within the promoter of the ST18 gene is hypermethylated in about 80% of the breast cancer samples and in the majority of breast cancer cell lines. The strong correlation between ST18 promoter hypermethylation and loss of ST18 expression in tumor cells suggests that this epigenetic mechanism is responsible for tumor-specific downregulation. We further show that ectopic ST18 expression in MCF-7 breast cancer cells strongly inhibits colony formation in soft agar and the formation of tumors in a xenograft mouse model.

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Acknowledgements

We thank Renate Frege, Konstanze Poppe, and Sabine Werner for excellent technical assistance, Christine von Klitzing for help in mutation analysis, and Peter Wassmuth for help in expression analysis. This work was supported by Deutsche Forschungsgemeinschaft grant Sche 373/4-1.

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Authors and Affiliations

  1. Department of Tumor Genetics, Max-Delbrück-Centre for Molecular Medicine, Berlin, 13092, Germany

    Burkhard Jandrig, Susanne Seitz, Arnfried Schwartz, Karin Ruecker & Siegfried Scherneck

  2. Signature diagnostics AG, Berlin, 10719, Germany

    Bernd Hinzmann & André Rosenthal

  3. atugen AG, Berlin, 13125, Germany

    Wolfgang Arnold

  4. Institute of Biochemistry and Biology, University Potsdam, Golm, 14476, Germany

    Burkhard Micheel

  5. Institute of Pathology, Charité Hospital, Humboldt University, Berlin, 10117, Germany

    Konrad Koelble

  6. Clinic of Surgery and Surgical Oncology, Robert Rössle Hospital, Berlin, 13122, Germany

    Konrad Koelble & Peter M Schlag

  7. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany

    Reiner Siebert

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  1. Burkhard Jandrig
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  2. Susanne Seitz
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  4. Wolfgang Arnold
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  5. Burkhard Micheel
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  12. André Rosenthal
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Correspondence to Burkhard Jandrig.

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Jandrig, B., Seitz, S., Hinzmann, B. et al. ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2. Oncogene 23, 9295–9302 (2004). https://doi.org/10.1038/sj.onc.1208131

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