An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice: a cytokine receptor superfamily oncogene.
A point mutation at codon 129 of the murine erythropoietin receptor (cEpoR) results in constitutive activation. We have generated a recombinant spleen focus-forming retrovirus in which the env gene is replaced by the cEpoR cDNA. Mice infected with this virus (but not by viruses expressing the wild-type EpoR) develop erythrocytosis and splenomegaly. From the spleen of infected animals we have isolated clonal, growth factor-independent, proerythroblast cell lines that express cEpoR, do not express the putative oncogene spi-1, and have rearranged and inactivated expression of the p53 suppressor oncogene. These cells induce erythroleukemia upon injection into mice. This demonstrates that oncogenic point mutations exist in a member of the cytokine receptor superfamily. The activated erythropoietin receptor does not transform cultured fibroblasts, suggesting why oncogenic mutations in other members of this receptor superfamily have not been detected.
Longmore
G D
GD
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Lodish
H F
HF
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D016207:Cytokines / Q000502:physiology; D004252:DNA Mutational Analysis; D005347:Fibroblasts; D015870:Gene Expression; D006133:Growth Substances / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009857:Oncogenes / Q000235:genetics; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016207:Cytokines; D006133:Growth Substances; D009838:Oligodeoxyribonucleotides; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53