Pigment-cell-specific genes from fibroblasts are transactivated after chromosomal transfer into melanoma cells.
Human and mouse fibroblast chromosomes carrying tyrosinase or b-locus genes were introduced, by microcell hybridization, into pigmented Syrian hamster melanoma cells, and the microcell hybrids were tested for transactivation of the fibroblast tyrosinase and b-locus genes. By using species-specific PCR amplification to distinguish fibroblast and melanoma cDNAs, it was demonstrated that the previously silent fibroblast tyrosinase and b-locus genes were transactivated following chromosomal transfer into pigmented melanoma cells. However, transactivation of the mouse fibroblast tyrosinase gene was unstable in microcell hybrid subclones and possibly dependent on a second fibroblast locus that could have segregated in the subclones. This second locus was not necessary for transactivation of the fibroblast b-locus gene, thus demonstrating noncoordinate transactivation of fibroblast tyrosinase and b-locus genes. Transactivation of the fibroblast tyrosinase gene in microcell hybrids apparently is dependent on the absence of a putative fibroblast extinguisher locus for tyrosinase gene expression, which presumably is responsible for the extinction of pigmentation in hybrids between karyotypically complete fibroblasts and melanoma cells.
Powers
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Department of Genetics, University of Illinois College of Medicine, Chicago 60612.
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Davidson
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002875:Chromosomes / Q000502:physiology*; D006224:Cricetinae; D017931:DNA Primers; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D016376:Oligonucleotides, Antisense; D010860:Pigments, Biological / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D015533:Transcriptional Activation; D014162:Transfection
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D010860:Pigments, Biological; D014442:Monophenol Monooxygenase