The v-erb A oncogene causes repression of erythrocyte-specific genes and an immature, aberrant differentiation phenotype in normal erythroid progenitors.
We have compared the effects of the v-erb A oncogene on proliferation and differentiation of normal erythroid progenitors with those of tyrosine kinase oncogenes, e.g. v-sea. For this, a v-erb A retrovirus containing the neomycin resistance gene as a selectable marker or, alternatively, a v-erb A-ts v-sea retrovirus were used to infect normal bone marrow cells. V-erb A induced the outgrowth of immature, erythropoietin(EPO)-dependent erythroid cells from infected bone marrow which ceased to proliferate and disintegrated after 9 to 18 divisions. In contrast, ts-v-sea erythroblasts grew for the expected 25 to 40 population doublings in the absence of EPO. Transcription of the erythrocyte genes carbonic anhydrase II and erythrocyte anion transporter was significantly inhibited in v-erb A infected erythroblasts, indicating that v-erb A alone was sufficient for the repression of the erythrocyte-specific genes observed in AEV-transformed leukemic cells. A detailed analysis of the differentiation phenotype induced by v-erb A in erythroblasts (in the presence or absence of a temperature-inactivated ts sea oncogene) indicates that v-erb A-erythroblasts express a partially mature, aberrant phenotype characterized by the coexpression of mature and immature differentiation antigens. This phenotype clearly differs from that induced by tyrosine kinase oncogenes in erythroid cells.
Schroeder
C
C
Institute of Molecular Pathology, Vienna, Austria.
Raynoschek
C
C
Fuhrmann
U
U
Damm
K
K
Vennström
B
B
Beug
H
H
D000818:Animals; D000954:Antigens, Surface; D002256:Carbonic Anhydrases / Q000235:genetics*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004900:Erythroblasts / Q000166:cytology* / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D005347:Fibroblasts; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D000954:Antigens, Surface; D018774:Oncogene Proteins v-erbA; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D004921:Erythropoietin; D002256:Carbonic Anhydrases