Dickkopf-1 activates cell death in MDA-MB435 melanoma cells

Andrei M. Mikheev, Svetlana A. Mikheeva, Robert Rostomily, Helmut Zarbl

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Dickkopf-1 (DKK-1) is known inhibitor of the canonical Wnt pathway. Recent studies strongly suggested that activation of DKK-1 expression results in inhibition of cell tumorigenicity. Reduced levels of DKK-1 in melanomas were recently shown. However, it is not known if DKK-1 activation in melanoma cells will inhibit cell tumorigenicity. In the present study, we overexpressed DKK-1 in melanoma cell line MDA-MB435. We show that while DKK-1 did not affect cell growth in soft agar, weak but significant inhibition of tumorigenicity in nude mice in vivo was observed. Analysis of resulting tumors revealed activation of cell death. In tumors originating from cells transduced with DKK-1, tumor mass was permeated with areas of necrosis. In tumors, originated from control cells, areas of necrosis were limited to the central region, a common feature of large tumors growing in nude mice. TUNEL assay revealed that in tumors originating from cells transduced with DKK-1 apoptotic cells were detected along the border of necrotic and viable areas of the tumors indicating significant increase in apoptotic process. Thus, our results indicate that activation of DKK-1 in melanoma cells leads to activation of apoptosis in vivo and, thus, is incompatible with tumor growth in nude mice.

Original languageEnglish (US)
Pages (from-to)675-680
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume352
Issue number3
DOIs
StatePublished - Jan 19 2007

Keywords

  • Cell death
  • Dickkopf-1
  • Melanoma
  • Tumor suppressor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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