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Clear cell sarcoma (CCS) is associated with the EWS/ATF1 oncogene that is created by chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. The melanocytic character of CCS suggests that the microphthalmia-associated transcription factor (Mitf), a major inducer of melanocytic differentiation, may be miss-expressed in CCS. Accordingly, we show that the mRNA and protein of the melanocyte-specific isoform of Mitf (Mitf-M) are present in several cultured CCS cell lines (Su-ccs-1, DTC1, Kao, MST-1, MST-2 and MST-3). The above cell lines thus provide a valuable experimental resource for examining the role of Mitf-M in both CCS and melanocyte differentiation. Melanocyte-specific expression of Mitf-M is achieved via an ATF-dependent melanocyte-specific cAMP-response element in the Mitf-M promoter, and expression of Mitf-M in CCS cells suggests that EWS/ATF1 (a potent and promiscuous activator of cAMP-inducible promoters) may activate the Mitf-M promoter. Surprisingly, however, the Mitf-M promoter is not activated by EWS/ATF1 in transient assays employing CCS cells, melanocytes or nonmelanocytic cells. Thus, our results indicate that Mitf-M promoter activation may require an appropriate chromosomal context in CCS cells or alternatively that the Mitf-M promoter is not directly activated by EWS/ATF1.

Original publication




Journal article


Br J Cancer

Publication Date





1072 - 1078


Blotting, Western, Cell Differentiation, Chloramphenicol O-Acetyltransferase, DNA Primers, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Leucine Zippers, Melanocytes, Microphthalmia-Associated Transcription Factor, Neoplasm Proteins, Oncogene Proteins, Fusion, Plasmids, Polymerase Chain Reaction, Promoter Regions, Genetic, Protein Isoforms, RNA, Neoplasm, Sarcoma, Sarcoma, Clear Cell, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured