The melanocyte inducing factor MITF is stably expressed in cell lines from human clear cell sarcoma.
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.
Li
K K C
KK
Department of Biology, HK University of Science & Technology, Kowloon, HK, China.
Goodall
J
J
Goding
C R
CR
Liao
S-K
SK
Wang
C-H
CH
Lin
Y-C
YC
Hiraga
H
H
Nojima
T
T
Nagashima
K
K
Schaefer
K-L
KL
Lee
K A W
KA
D015153:Blotting, Western; D002454:Cell Differentiation; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016350:Leucine Zippers; D008544:Melanocytes / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms; D012334:RNA, Neoplasm / Q000032:analysis; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018227:Sarcoma, Clear Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; C111598:EWS-ATF1 fusion protein, human; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase