v-src induces clonal sarcomas and rapid metastasis following transduction with a replication-defective retrovirus.
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 approximately 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.
Stoker
A W
AW
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California 94720.
Sieweke
M H
MH
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D001483:Base Sequence; D002645:Chickens; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D005822:Genetic Vectors; D009362:Neoplasm Metastasis; D021141:Nucleic Acid Amplification Techniques; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis; D009857:Oncogenes; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D001357:Sarcoma, Avian / Q000235:genetics* / Q000473:pathology; D014161:Transduction, Genetic; D014779:Virus Replication
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D015688:Oncogene Protein pp60(v-src)