The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma

Br J Cancer. 2003 Sep 15;89(6):1072-8. doi: 10.1038/sj.bjc.6601212.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • DNA Primers
  • DNA-Binding Proteins
  • EWS-ATF1 fusion protein, human
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Protein Isoforms
  • RNA, Neoplasm
  • Transcription Factors
  • Chloramphenicol O-Acetyltransferase