Amplification and altered expression of the c-myc oncogene in A-MuLV-transformed fibroblasts.
Chromosomal rearrangements involving the c-myc oncogene are a prevalent feature of plasmacytomas that arise after inoculating BALB/c mice with pristane and Abelson murine leukaemia virus (A-MuLV). With this observation in mind, we decided to determine if any genetic alterations of the c-myc locus could be observed in cells of a different type, when transformed in vitro by A-MuLV. Here we have analysed three independent A-MuLV-transformed NIH 3T3 lines (ANN-I, 54c12 and N25), and found that the c-myc locus is amplified 8-19-fold in each transformant. Quantitative S1 nuclease mapping performed on ANN-I and 54c12 RNAs demonstrated that: (1) c-myc messenger RNAs accumulated to double the levels found in NIH 3T3 cells; and (2) a shift in the use of the two normal c-myc transcription initiation sites (P1 and P2) occurred in favour of the 3' site, P2. Analysis of c-myc chromatin by DNase I treatment of 54c12 nuclei revealed that most, if not all, of the c-myc gene copies were transcriptionally competent. We present alternative ideas to explain why amplification of the c-myc gene occurs repeatedly in A-MuLV-transformed fibroblasts. Finally, we discuss our results in relation to the hypothesis linking the phenomenon of tumour progression with the amplification of oncogenes.
D000011:Abelson murine leukemia virus / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004262:DNA Restriction Enzymes / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005784:Gene Amplification; D005786:Gene Expression Regulation; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013729:Terpenes / Q000494:pharmacology
D013729:Terpenes; C009042:pristane; D004720:Endonucleases; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I; D015719:Single-Strand Specific DNA and RNA Endonucleases