V-src Induces Clonal Sarcomas and Rapid Metastasis Following Transduction with a Replication-Defective Retrovirus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 24; pp. 10123 - 10127
• Main Authors: Stoker, Andrew W., Sieweke, Michael H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1989; National Acad Sciences
• Subjects: 550200 - Biochemistry; Animals; ANTIGENS; AUTORADIOGRAPHY; Avian Sarcoma Viruses - genetics; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; CARCINOGENESIS; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chickens; DAYS LIVING RADIOISOTOPES; Defective Viruses - genetics; Defective Viruses - physiology; DISEASES; DNA; DNA POLYMERASES; DNA, Neoplasm - analysis; DNA, Neoplasm - genetics; ENZYMES; ETIOLOGY; Fundamental and applied biological sciences. Psychology; GENE AMPLIFICATION; Gene Expression; GENES; Genetic Vectors; ISOTOPES; LIGHT NUCLEI; Liver; METASTASES; MICROORGANISMS; Molecular and cellular biology; Neoplasm Metastasis; NEOPLASMS; Nodules; NUCLEI; Nucleic Acid Amplification Techniques; NUCLEIC ACIDS; NUCLEOTIDYLTRANSFERASES; ODD-ODD NUCLEI; Oncogene Protein pp60(v-src) - analysis; ONCOGENES; ONCOGENIC VIRUSES; ORGANIC COMPOUNDS; Packaging; PARASITES; PATHOGENESIS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; PHOSPHORUS-GROUP TRANSFERASES; Polymerase chain reaction; POLYMERASES; RADIOISOTOPES; Restriction Mapping; RNA Splicing - genetics; RNA, Messenger - genetics; Sarcoma; Sarcoma, Avian - genetics; Sarcoma, Avian - pathology; SARCOMAS; Transduction, Genetic; TRANSFERASES; Tumors; Virus Replication; VIRUSES; Sarcoma; Nucleotide sequence; Induction; V-Onc gene; Retroviridae; Histology; Metastasis; Virus; Animal; Tumor; Transduction; Southern blotting; Vector
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.24.10123

v-src is an effective carcinogen when expressed from Rous sarcoma virus (RSV) in vivo. Whereas RSV tumors require sustained oncogene expression, their growth is largely a balance between viral recruitment of tissues and host immune destruction of infected cells. We have therefore examined the tumorigenic potential of v-src in the absence of viral recruitment and viral antigen expression. v-src was introduced with high efficiency into chicken wing web tissues using replication-defective (rd) retroviral vectors. Clonal sarcomas were induced rapidly, and, furthermore, v-src potentiated metastatic progression in ≈ 0.1%-1% of tumor clones with unexpectedly short latency. rd vectors proved effective not only in transducing v-src into tissues but also as insertional markers of tumor clonality. The rd vector present in most primary and metastatic tumors was a highly truncated form of RSV derived by viral transmission of spliced v-src mRNA; this vector should thus avoid viral recruitment and host anti-viral immune reaction through its complete lack of viral structural genes. Under such conditions v-src maintains strong carcinogenicity in vivo when restricted to clonal tumor growth and can confer rapid metastatic potential on a discrete subset of tumor clones.