Regulation of expression of MSG1 melanocyte-specific nuclear protein in human melanocytes and melanoma cells.
MSG1 is a nuclear protein and a possible transcriptional transactivator that is expressed strongly in melanocytes but very weakly, if at all, in most nonmelanocytic cells or adult mouse tissues. This strong expression of MSG1 in cultured normal human epidermal melanocytes was found to be dependent on both endothelin-1 and FGF-2. The phorbol ester TPA could be substituted for endothelin-1. The MSG1 mRNA transcripts were rapidly induced by either endothelin-1 or TPA. However, FGF-2 had no effects at the mRNA level, suggesting its contribution at the translational and/or posttranslational level(s). MSG1 (as well as its mRNA transcripts) was induced by TPA in human melanoma cells, which produce FGF-2 as an autocrine growth factor. Melanoma cells derived from primary tumors or tyrosinase-positive metastatic melanoma cells expressed MSG1 after TPA treatment, while tyrosinase-negative metastatic melanoma cells or nonmelanocytic cells did not. This TPA-induced MSG1 expression in melanoma cells correlated with the expression of the MSG1 mRNA transcripts and TPA-dependent transcriptional activation of the MSG1 promoter sequence, indicating its transcriptional regulation. In vivo, MSG1 protein was detected in human nevocytic nevus confined to the pigmented region, while MSG1 expression showed cell-level heterogeneity in pigmented melanoma tissues. These results demonstrate that MSG1 expression is regulated transcriptionally and posttranscriptionally by local growth factors as well as by the cellular status of differentiation.
Li
H
H
MGH Cancer Center, Massachusetts General Hospital-East, Charlestown, Massachusetts, 02129, USA.
Ahmed
N U
NU
Fenner
M H
MH
Ueda
M
M
Isselbacher
K J
KJ
Shioda
T
T
D051017:Apoptosis Regulatory Proteins; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C512688:CITED1 protein, human; D002273:Carcinogens; D003470:Culture Media; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate