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.
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 pp60src encoded by Rous sarcoma virus, we constructed a new recombinant virus, Mo-MuLV(+ src). Mo-MuLV(+ src) encodes pp60src 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 pp60src 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.
Feuerman
M H
MH
Department of Molecular Biology and Biochemistry, University of California, Irvine.
Lee
W T
WT
Pattengale
P K
PK
Fan
H
H
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000472:pathogenicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics*; D015688:Oncogene Protein pp60(v-src); D009857:Oncogenes; D011233:Precipitin Tests; D012191:Retroviridae Proteins / Q000235:genetics*; D014162:Transfection; D010948:Viral Plaque Assay
D004279:DNA, Viral; D012191:Retroviridae Proteins; D015688:Oncogene Protein pp60(v-src)