Transcriptional activation of cKi-ras proto-oncogene resulting from retroviral promoter insertion.
Enhanced expression of the cKi-ras proto-oncogene in a bone marrow-derived mouse cell line, 416B, has been shown to be associated with the integration of Friend viral DNA into the cellular gene. Here we report the results of experiments designed to clarify the molecular mechanism responsible for the cKi-ras overexpression. Based on primer extension analyses and DNA sequencing of cKi-ras cDNA clones, we have obtained evidence that the 416B cells contain viral-host chimaeric transcripts that initiate within the 3' long terminal repeat (LTR) of the integrated provirus. Processing of the transcripts from the rearranged cKi-ras gene includes an unexpected splicing event associated with the fortuitous creation of a cryptic donor splice site at the junction between the proviral and cellular DNA sequences. These data demonstrate that enhanced cKi-ras expression in the 416B cells results from a retroviral promoter insertion mechanism of transcriptional activation.
Trusko
S P
SP
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6072.
Hoffman
E K
EK
George
D L
DL
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow; D002460:Cell Line; D004251:DNA Transposable Elements; D005091:Exons; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D015533:Transcriptional Activation
D004251:DNA Transposable Elements; C000715470:MAS1 protein, human; D015345:Oligonucleotide Probes; D000090063:Proto-Oncogene Mas