Transformation of murine pre-B-lymphocytes by v-erb-B: progression to growth factor independence and tumorigenicity.
v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia.
Miller
M
M
Leukemia Research and Viral Pathology Unit, Children's Medical Research Foundation, Camperdown, Sydney, NSW, Australia.
Kennewell
A
A
Symonds
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005814:Genes, Viral / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012334:RNA, Neoplasm / Q000032:analysis
D012334:RNA, Neoplasm; D016173:Macrophage Colony-Stimulating Factor