Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1038/sj.bjc.6601212

Type

Journal article

Journal

Br J Cancer

Publication Date

15/09/2003

Volume

89

Pages

1072 - 1078

Keywords

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