Deregulated Expression of an Activated Allele of Human c-myc in Transfected Fibroblast Cultures

Abstract

BL tumors characteristically exhibit chromosomal rearrangements involving the c-myc gene and one of the Ig loci. In these cells, the translocated myc allele is deregulated (or “activated”) in such a way that it is expressed constitutively. The normal allele, by contrast, is either transcriptionally silent or is expressed at very low levels (1). We are analyzing the mechanisms by which c-myc expression is altered in cells of the Ramos BL tumor. Genomic clones representing either a wild-type (germline) c-myc allele or the IgH-myc translocation locus (2) from Ramos tumor cells were cloned in the vector pSV2.gpt (3) (fig. 1). In parallel gene transfer experiments these constructs were transfected into the rat fibroblast cell line FR3T3. Stably transfected, clonal cell lines bearing intact human c-myc genes were assayed for their ablity to regulate expression of the introduced alleles in response to serum in density-arrested cultures. Modulation of c-myc activity by serum is characteristic of the normal gene in established fibroblast cell lines (4).