1. ¹Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany
2. ²Department of Medicine, University of North Carolina, USA
3. ³Internal Medicine I, University of Regensburg, D-93053 Regensburg, Germany

Correspondence: A Bosserhoff, E-mail: anja.bosserhoff@klinik.uni-regensburg.de

⁴These authors contributed equally to this work

Received 18 July 2003; Revised 22 April 2004; Accepted 23 April 2004; Published online 20 September 2004.

Abstract

Malignant transformation of melanocytes frequently coincides with loss of E-cadherin expression. Here, we show that loss of E-cadherin leads to induction of nuclear factor kappa B (NFB) activity in melanoma cell lines. Melanoma cells show constitutively active NFB, whereas no activity is found in primary melanocytes. After re-expression of E-cadherin in melanoma cells, strong downregulation of NFB activity was found. Consistently, NFB activity was induced in primary human melanocytes after inhibition of E-cadherin activity by functionally blocking anti-E-cadherin antibodies. Interestingly, re-expression of E-cadherin-blocked p38 MAPK activity and the p38 MAPK inhibitors SB203580 and SB202190 almost completely prevented NFB activation in melanoma cells. Furthermore, cytoplasmatic -catenin induced p38 and NFB activation in malignant melanoma. To our knowledge, this is the first report suggesting a correlation between E-cadherin and NFB activity in melanocytes and melanoma cells. In summary, we conclude that loss of E-cadherin and cytoplasmatic -catenin induces p38-mediated NFB activation, potentially revealing an important mechanism of tumorigenesis in malignant melanomas.