The nuclear oncogenes v-erbA and v-ets cooperate in the induction of avian erythroleukemia.
The nuclear oncogenes v-erbA and v-ets are known to cooperate with other viral oncogenes in the induction of avian erythroleukemia. Thus, in the case of avian erythroblastosis virus (AEV), v-erbA enhances the effect of the tyrosine kinase-encoding v-erbB oncogene by blocking the terminal differentiation of erythroid cells. In the case of E26 virus a fusion of the product from v-ets to that of the nuclear oncogene v-myb is a prerequisite for leukemogenicity. Here we show that an artificial virus carrying both v-erbA and v-ets induces a rapid, acute erythroleukemia phenotypically similar to that induced by AEV. In contrast, virus constructs containing either v-erbA or v-ets alone are non-leukemogenic, although they are capable of transforming erythroid cells in vitro. Analysis of in vitro-transformed cells showed that v-erbA induces a block of differentiation without abrogating dependence on anemic serum, while v-ets predominantly causes anemic serum independence. As expected, cells transformed by both oncogenes exhibit an increased proliferative potential, are blocked in differentiation and are anemic serum independent. These data demonstrate that two separately expressed nuclear oncoproteins can complement each other in vitro and in vivo. They also show that the v-Ets protein on its own can contribute to leukemogenesis.
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
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D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D002645:Chickens; D015870:Gene Expression; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology*; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*
D009687:Nuclear Proteins; D018774:Oncogene Proteins v-erbA; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic; C050379:oncogene proteins v-ets