Document 0073
 DOCN  M9460073
 TI    A constitutively activated erythropoietin receptor stimulates
       proliferation and contributes to transformation of multipotent,
       committed nonerythroid and erythroid progenitor cells.
 DT    9404
 AU    Longmore GD; Pharr PN; Lodish HF; Department of Medicine, Washington
       University, St. Louis,; Missouri 63110.
 SO    Mol Cell Biol. 1994 Apr;14(4):2266-77. Unique Identifier : AIDSLINE
       MED/94187697
 AB    If the env gene of spleen focus-forming virus (SFFV) is replaced by a
       cDNA encoding a constitutively active form of the erythropoietin
       receptor, EPO-R(R129C), the resultant recombinant virus, SFFVcEPO-R,
       induces transient thrombocytosis and erythrocytosis in infected mice.
       Clonogenic progenitor cell assays of cells from the bone marrow and
       spleens of these infected mice suggest that EPO-R(R129C) can stimulate
       proliferation of committed megakaryocytic and erythroid progenitors as
       well as nonerythroid multipotent progenitors. From the spleens of
       SFFVcEPO-R-infected mice, eight multiphenotypic immortal cell lines were
       isolated and characterized. These included primitive erythroid,
       lymphoid, and monocytic cells. Some expressed proteins characteristic of
       more than one lineage. All cell lines resulting from SFFVcEPO-R
       infection contained a mutant form of the p53 gene. However, in contrast
       to infection by SFFV, activation of PU.1 gene expression, by retroviral
       integration, was not observed. One cell line had integrated a provirus
       upstream of the fli-1 gene, in a location typically seen in
       erythroleukemic cells generated by Friend murine leukemia virus
       infection. This event led to increased expression of fli-1 in this cell
       line. Thus, infection by SFFVcEPO-R can induce proliferation and lead to
       transformation of nonerythroid as well as very immature erythroid
       progenitor cells. The sites of proviral integration in clonal cell lines
       are distinct from those in SFFV-derived lines.
 DE    Animal  Blood Platelets/*CYTOLOGY  Bone Marrow/CYTOLOGY/PHYSIOLOGY  Cell
       Division  Cell Line  *Cell Transformation, Viral  Comparative Study
       Erythrocyte Count  Erythrocytes/*CYTOLOGY  Female  *Genes, env
       Hematopoietic Stem Cells/*CYTOLOGY/PHYSIOLOGY  Leukemia,
       Experimental/BLOOD  Mice  Mice, Inbred BALB C  Mice, Inbred Strains
       Platelet Count  Receptors, Erythropoietin/BIOSYNTHESIS/*PHYSIOLOGY
       Retroviridae Infections/BLOOD  Spleen/CYTOLOGY/PHYSIOLOGY  Spleen
       Focus-Forming Viruses/*GENETICS  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Tumor Virus
       Infections/BLOOD  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).