Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 1, pp 118–128

The Ets-1 transcription factor is involved in the development and invasion of malignant melanoma

Authors

  • T. Rothhammer
    • Institute of PathologyUniversity of Regensburg
  • J. C. Hahne
    • Institute of PathologyUniversity of Bonn
  • A. Florin
    • Institute of PathologyUniversity of Bonn
  • I. Poser
    • Institute of PathologyUniversity of Regensburg
  • F. Soncin
    • CNRS UMR8526, Institut de Biologie de Lille
    • Institute of PathologyUniversity of Bonn
  • A.-K. Bosserhoff
    • Institute of PathologyUniversity of Regensburg
Research Article

DOI: 10.1007/s00018-003-3337-8

Cite this article as:
Rothhammer, T., Hahne, J.C., Florin, A. et al. CMLS, Cell. Mol. Life Sci. (2004) 61: 118. doi:10.1007/s00018-003-3337-8

Abstract

The Ets-1 transcription factor plays a role in tumor vascularization and invasion by regulating expression of matrix-degrading proteases in endothelial cells and fibroblasts in the tumor stroma. During early embryogenesis, Ets-1 is expressed in migrating neural crest cells from which melanocytes arise. In the present study, we analyzed Ets-1 expression in various melanocytic lesions and investigated its functional importance in malignant melanomas. We found that Ets-1 was upregulated both in vivo and in vitro in malignant melanoma, compared to benign melanocytic lesions and to primary melanocytes. Assessment of DNA-binding and transactivation assays documented a strong Ets activity in melanoma cells. Using an antisense strategy, the expression and activity of Ets-1 were reduced in the melanoma cell line Mel Im. This correlated with a diminished expression of several Ets-1 target genes known to be involved in invasion, such as MMP1, MMP3, uPA and integrin β3. In line with these findings, the invasive potential of the melanoma cells measured in a Boyden Chamber model was reduced up to 60% after Ets-1 blockade. This can be attributed to the role of Ets-1 in transcriptional regulation of factors involved in invasion of melanoma cells. We conclude that over-expression of Ets-1 during melanoma development contributes to the malignant phenotype.

Malignant melanoma Ets-1 proliferation migration invasion

Copyright information

© Birkhäuser-Verlag Basel 2004