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A more recent version of this article appeared on June 29, 2001
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M011224200v1
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Papers In Press, published online ahead of print April 25, 2001
J. Biol. Chem, 10.1074/jbc.M011224200
Submitted on December 13, 2000
Revised on April 24, 2001
Accepted on April 25, 2001

Loss of E-cadherin expression in melanoma cells involves upregulation of the transcriptional repressor Snail

Ina Poser, David Domínguez, Antonio G. de Herreros, Alinda Varnai, Reinhard Buettner, and Anja K. Bosserhoff

Institute of Pathology, RWTH Aachen, Aachen 52074

Corresponding Author: bosserhoff{at}pat.rwth-aachen.de

Malignant transformation of melanocytes frequently coincides with loss of E-Cadherin expression. Here we show that loss of E-Cadherin in melanoma cell lines does not involve mutations in the E-Cadherin gene, promoter methylation or alterations in expression of AP-2 transcription factors as suggested previously. In a panel of different melanoma cell lines E-Cadherin expression was negatively regulated by upregulation of the transcription factor Snail. In comparison to primary human melanocytes, where Snail expression was not detected by RT-PCR, significant expression was found in all eight melanoma cell lines. In parallel, western blot and RT-PCR analysis revealed strong reduction of E-Cadherin expression in the melanoma cells. Consistently, transient transfection of a Snail expression plasmid into human primary melanocytes led to significant downregulation of E-Cadherin, whereas transient and stable transfection of an antisense snail construct induced reexpression of E-Cadherin in Mel Ju and Mel Im melanomas. In summary, we conclude that activation of Snail expression plays an important role in downregulation of E-Cadherin and tumorigenesis of malignant melanomas.


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