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

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 beta3. 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.

• Authors: T Rothhammer, J C Hahne, A Florin, I Poser, F Soncin, N Wernert, A-K Bosserhoff
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 61 Issue 1 Pg. 118-28 (Jan 2004) ISSN: 1420-682X [Print] Switzerland
• PMID: 14704859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• ETS1 protein, human
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-ets
• Transcription Factors
• Protein-Tyrosine Kinases

Topics

• DNA, Neoplasm (metabolism)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization
• Melanocytes (pathology)
• Melanoma (genetics, pathology)
• Neoplasm Invasiveness
• Protein-Tyrosine Kinases (genetics, metabolism)
• Proto-Oncogene Protein c-ets-1
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins c-ets
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic (genetics)
• Tumor Cells, Cultured