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 methylat ion, or alterations in expression of AP-2 transcription factors as suggeste d previously. In a panel of different melanoma cell lines, E-cadherin expre ssion was negatively regulated by up-regulation of the transcription factor Snail. In comparison with primary human melanocytes, where Snail expressio n was not detected by reverse transcription-polymerase chain reaction, sign ificant 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. C onsistently, transient transfection of a Snail expression plasmid into huma n primary melanocytes led to significant down-regulation of E-cadherin, whe reas transient and stable transfection of an antisense Snail construct indu ced 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.