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

被引:101
作者
Rothhammer, T
Hahne, JC
Florin, A
Poser, I
Soncin, F
Wernert, N
Bosserhoff, AK
机构
[1] Univ Bonn, Inst Pathol, D-53127 Bonn, Germany
[2] Univ Regensburg, Inst Pathol, D-93042 Regensburg, Germany
[3] Inst Biol Lille, CNRS, UMR 8526, F-59021 Lille, France
关键词
malignant melanoma; Ets-1; proliferation; migration; invasion;
D O I
10.1007/s00018-003-3337-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:118 / 128
页数:11
相关论文
共 52 条
[51]  
WERNERT N, 1994, CANCER RES, V54, P5683
[52]  
WERNERT N, 1992, AM J PATHOL, V140, P119