TY - JOUR
T1 - An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice
T2 - A cytokine receptor superfamily oncogene
AU - Longmore, Gregory D.
AU - Lodish, Harvey F.
N1 - Funding Information:
We thank Dr. Jing-Po Li for reagents and helpful discussions throughout the course of this work. We are grateful to Drs. Alan Bernstein and Robert Weinberg for critically reading the manuscript. We also thank Douglas Hilton, Drorit Neumann, Stephanie Watowich, and Akihiko Yoshimura for constant criticisms and discussions. This work was supported by National Institutes of Health/National Institute on Aging Physician Scientist Award AGO0294 to G. D. L. and National Institutes of Health grant HL32262 to H. F. L.
PY - 1991/12/20
Y1 - 1991/12/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026326555&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(91)90286-8
DO - 10.1016/0092-8674(91)90286-8
M3 - Article
C2 - 1662116
AN - SCOPUS:0026326555
SN - 0092-8674
VL - 67
SP - 1089
EP - 1102
JO - Cell
JF - Cell
IS - 6
ER -