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Comparison of three recombinant murine leukemia viruses carrying the v‐src oncogene of avian sarcoma virus: Differences in in vitro transformation and in vivo pathogenicity
Author(s) -
Feuerman Miriam H.,
Lee William T.L.,
Pattengale Paul K.,
Fan Hung
Publication year - 1988
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940010112
Subject(s) - biology , virology , transformation (genetics) , recombinant dna , in vitro , virus , leukemia , in vivo , viral transformation , murine leukemia virus , oncogene , proto oncogene tyrosine protein kinase src , sarcoma , oncovirus , pathogenicity , microbiology and biotechnology , cancer , genetics , gene , receptor , cell cycle , medicine , pathology
We previously described a recombinant Moloney murine leukemia virus (Mo‐MuLV) carrying the v‐ src oncogene, Mo‐MuLV( src ). Mo‐MuLV( src ) encodes a gag‐ src fusion protein, transforms cells in culture, and induces fibrosarcomas in vivo. To compare transforming properties of the gag‐ src fusion protein to pp60 src encoded by Rous sarcoma virus, we constructed a new recombinant virus, Mo‐MuLV(+ src ). Mo‐MuLV(+ src ) encodes pp60 src in the context of Mo‐MuLV. Cells transformed by Mo‐MuLV(+ src ) were round and formed colonies in soft agar, whereas Mo‐MuLV( src )‐infected cells were fusiform and did not grow in suspension. Thus, the extent of transformation induced by Mo‐MuLV(+ src ) was greater than that induced by Mo‐MuLV( src ). Subcutaneous inoculation of either virus into neonatal NIH Swiss mice resulted in fibrosarcomas at the site of injection. Further studies indicated that tumors induced by Mo‐MuLV(+ src ) grew rapidly but rarely metastasized. In contrast, tumors induced by Mo‐MuLV( src ) grew somewhat more slowly but metastasized with a high frequency (60%). These viruses may provide a useful model system for tumor metastasis. Another src ‐containing virus was also studied, MRSV (constructed by Anderson and Scolnick). MRSV also encodes pp60 src but in the context of amphotropic MuLV. When injected intravenously into six‐week‐old mice, MRSV induced splenomegaly and spleen foci but no solid tumors, as reported previously. In contrast, Mo‐MuLV( src )‐induced fibrosarcomas mostly in the spleen under the same inoculation protocol. These results suggest that the v‐ src oncogene was the major pathogenic determinant in neonatal mice for all three src ‐containing viruses; however, variations in the nature of the transforming protein modulated the behavior of the induced tumors. In adult mice, greater differences in pathogenicity were observed.