Identification of a provirally activated c-Ha-ras oncogene in an avian nephroblastoma via a novel procedure: cDNA cloning of a chimaeric viral-host transcript.
Retrovirus without oncogenes often exert their neoplastic potential as insertional mutagens of cellular proto-oncogenes. This may be associated with the production of chimaeric viral-host transcripts; in these cases; activated cellular genes can be identified by obtaining cDNA clones of bipartite RNAs. This approach was used in the analysis of chicken nephroblastomas induced by myeloblastosis-associated virus (MAV). One tumor contained a novel mRNA species initiated within a MAV LTR. cDNA cloning revealed that this mRNA encodes a protein of 189 amino acids, identical to that of normal human Ha-ras-1 at 185 positions, including positions implicated in oncogenic activation of ras proto-oncogenes; there are no differences between the coding sequences of presumably normal Ha-ras cDNA clones from chicken lymphoma RNA and the tumor-derived cDNAs. The chimaeric mRNA in the nephroblastoma is at least 25-fold more abundant than c-Ha-ras mRNA in normal kidney tissue, and a 21-kd ras-related protein is present in relatively large amounts in the tumor. We conclude that a quantitative change in c-Ha-ras gene expression results from an upstream insertion mutation and presumably contributes to tumorigenesis in this single case. Little or no increase in c-Ha-ras RNA or protein was observed in other nephroblastomas.
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D009189:Avian Myeloblastosis Virus / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes; D005814:Genes, Viral; D008223:Lymphoma / Q000382:microbiology; D051379:Mice; D009857:Oncogenes; D012334:RNA, Neoplasm / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic; D009396:Wilms Tumor / Q000382:microbiology*
D012334:RNA, Neoplasm; D012367:RNA, Viral; D004247:DNA; D004262:DNA Restriction Enzymes