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Expression of Dickkopf genes is strongly reduced in malignant melanoma

Abstract

The Dickkopf (DKK) genes were originally identified as factors inducing head formation in Xenopus. The genes code for inhibitors that are involved in Wnt signaling. We speculate that loss of DKK expression plays a role in development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of DKK, especially DKK-3 transcription. We found that DKK-1, -2 and -3 were downregulated or lost in all cell lines and in most of the tumor samples analysed. Reduced DKK-3 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription–polymerase chain reaction RT–PCR analysis. Functional assays with stable DKK-3 transfected cell lines revealed that DKK-3 expression increased cell-cell adhesion and decreased cell migration. Further, downregulation of fibronectin, snail-1 and re-expression of E-cadherin was found in the DKK-3 expressing cell clones supporting a role of DKK-3 in tumor progression. Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression.

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Acknowledgements

We are indebted to Dr J Johnson (University of Munich, Germany) for providing melanoma cell lines and to Susanne Wallner for excellent technical assistance. This work was supported in part by grants from the DFG and the Deutsche Krebshilfe to AB

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Correspondence to A K Bosserhoff.

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Kuphal, S., Lodermeyer, S., Bataille, F. et al. Expression of Dickkopf genes is strongly reduced in malignant melanoma. Oncogene 25, 5027–5036 (2006). https://doi.org/10.1038/sj.onc.1209508

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Keywords

  • Dickkopf
  • tumor-suppressor gene
  • Wnt signaling
  • malignant melanoma
  • cancer

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