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PMID: 3011401 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

The EMBO journal ·Vol. 5 ·No. 2 ·1986-02-00 ·Pages 301-9

Westaway D, Papkoff J, Moscovici C, Varmus HE

Abstract

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.

MeSH Terms
Animals Avian Leukosis Virus/genetics Avian Myeloblastosis Virus/genetics Base Sequence Chickens Cloning, Molecular DNA/analysis DNA Restriction Enzymes Genes, Viral Lymphoma/microbiology Mice Oncogenes RNA, Neoplasm/genetics RNA, Viral/genetics Transcription, Genetic Wilms Tumor/microbiology
Chemicals
RNA, Neoplasm RNA, Viral DNA DNA Restriction Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Westaway D
Papkoff J
Moscovici C
Varmus H E
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1986-02-00
Pages
301-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1166733
Subset
IM
Databases
GENBANK
X03578
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