Proviral-activated c-erbB is leukemogenic but not sarcomagenic: characterization of a replication-competent retrovirus containing the activated c-erbB.
Avian leukosis virus (ALV) induces erythroblastosis in chickens by integrating its DNA into the host c-erbB locus and by activating expression of truncated c-erbB transcripts. Although there is a 100% correlation of c-erbB activation with ALV-induced erythroblastosis, direct evidence that the activated c-erbB is oncogenic has not been established. We have constructed a replication-competent retrovirus containing the activated c-erbB to investigate its transforming potential. The Rous c-erbB virus (REB-c) was constructed by inserting the activated c-erbB cDNA into a Rous sarcoma virus vector in place of src. When transfected into transformed quail fibroblasts (QT6), the REB-c construct stably integrates and expresses c-erbB-specific transcripts and produces infectious virus. The REB-c retrovirus produces short-latency polyclonal erythroblastosis in chickens. However, in contrast to avian erythroblastosis virus which contains v-erbB, the REB-c construct does not transform chicken embryo fibroblasts in vitro, nor does the REB-c virus produce sarcomas when injected into the wing web of chickens. Our results provide the first direct evidence that the activated c-erbB which lacks the amino-terminal extracellular domain but which retains the entire carboxy-terminal sequences is leukemogenic but not sarcomagenic.
Pelley
R J
RJ
Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Moscovici
C
C
Hughes
S
S
Kung
H J
HJ
D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D001353:Avian Leukosis / Q000235:genetics; D001354:Avian Leukosis Virus / Q000235:genetics*; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D004247:DNA / Q000032:analysis; D007942:Leukemia, Experimental / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011533:Proviruses / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000235:genetics*; D014162:Transfection
D011518:Proto-Oncogene Proteins; D004247:DNA