Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail.
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 up-regulation of the transcription factor Snail. In comparison with primary human melanocytes, where Snail expression was not detected by reverse transcription-polymerase chain reaction, significant expression was found in all eight melanoma cell lines. In parallel, Western blot and reverse transcription-polymerase chain reaction 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 down-regulation 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 down-regulation of E-cadherin and tumorigenesis of malignant melanomas.
Poser
I
I
Institute of Pathology, Medical School Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, D-52074 Aachen, Germany.
Domínguez
D
D
de Herreros
A G
AG
Varnai
A
A
Buettner
R
R
Bosserhoff
A K
AK
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008745:Methylation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015820:Cadherins; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D000071250:Snail Family Transcription Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors