cis activation of the c-myc gene in bovine papilloma virus type 1/human c-myc hybrid plasmids.
The c-myc gene amplification observed in human tumors is likely to represent an activation mechanism aiming at an increased transcription level. In order to evaluate the biological significance of this amplification in the malignant transformation we have designed an experimental model that could possibly mimic this situation in vitro. We have constructed a series of plasmids which physically link the human c-myc gene to the bovine papilloma virus type 1 genome (BPV1) and therefore should be maintained as amplified episomes upon transformation of rodent cells. Anticipating that the high copy number will bring about the immortalizing capacity of the c-myc gene, the constructions were introduced into primary rat embryo cells. Immortal cell lines were established by transfection of the hybrid plasmids carrying either the complete BPV1 genome or the transforming region of the viral genome. The BPV1 DNA alone or the c-myc gene alone has no activity in this assay. The analysis of the established cell lines demonstrates that the transfected plasmids are present not as free copies as anticipated but rather integrated as tandem repeats. We present data which strongly suggest that the immortalization capacity of the hybrid plasmids reflects the activation of the c-myc gene by the transactivable BPV1 enhancer. Although both the BPV1 early genes and the c-myc gene are actively transcribed, most of the cell lines do not display a transformed phenotype.
Modjtahedi
N
N
Laboratoire d'Oncologie Moléculaire, Institut Gustave Roussy, Villejuif, France.
Feunteun
J
J
Brison
O
O
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D002460:Cell Line; D005091:Exons; D005784:Gene Amplification; D005814:Genes, Viral; D006801:Humans; D051379:Mice; D027383:Papillomaviridae / Q000235:genetics*; D010957:Plasmids; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D014162:Transfection