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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Mikheev AM,Mikheeva SA,Rostomily R,Zarbl H

doi

10.1016/j.bbrc.2006.11.079

subject

Has Abstract

pub_date

2007-01-19 00:00:00

pages

675-80

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)02550-2

journal_volume

352

pub_type

杂志文章

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