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

Rothhammer, T. and Hahne, J. C. and Florin, A. and Poser, I. and Soncin, F. and Wernert, N. and Bosserhoff, Anja-Katrin (2004) The Ets-1 transcription factor is involved in the development and invasion of malignant melanoma. CELLULAR AND MOLECULAR LIFE SCIENCES, 61 (1). pp. 118-128. ISSN 1420-682X

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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.

Item Type: Article
Uncontrolled Keywords: ENDOTHELIAL-CELLS; PLASMINOGEN-ACTIVATOR; MOLECULAR-BIOLOGY; EPITHELIAL-CELLS; TUMOR INVASION; MESSENGER-RNA; RETINOIC ACID; BREAST-CANCER; GENE FAMILY; EXPRESSION; malignant melanoma; Ets-1; proliferation; migration; invasion
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 Aug 2021 08:09
Last Modified: 04 Aug 2021 08:09
URI: https://pred.uni-regensburg.de/id/eprint/38127

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