(1) A recombinant murine retrovious vector containing the v-erbB gene of avian erythroblastosis virus was generated and transformed a variety of established mammalian cell lines. The murine erbB virus was also capable of abrogating the EGF-dependence of murine epithelial cells and induced pre-B lyphoid transformation in a murine bone marrow colony-forming assay. (2) To more clearly define the characteristics of hematopoietic cell populations transformed by ras, src, fes and abl oncogenes, continuous clonal cell lines established in our laboratory were examined for phenotypic and functional markers specific to various hematopoietic lineages. The majority of transformed cell lines, irrespective of the oncogene-containing retrovirus used for their induction, possessed characteristics of immature B lymphocytes. However, some ras-induced transformants coexpressed early B lymphoid and myeloid antigens and could be manipulated to differentiate along either pathway. These results suggest that a multipotential progenitor cell may exist which is a target for ras-induced transformation and supports the hypothesis of a close developmental relationship between B lymphoid and myeloid lineages. (3) A long-term interleukin-3 (IL-3)-dependent basophilic cell line was utilized to investigate the mechanisms involved in conversion to a factor-independent neoplastic state. Abrogation of IL-3 dependence occurred spontaneously at very low frequency and at a very high frequency after infection with tyrosine kinase-coding retroviral oncogenes. In all cases, release of factor dependence correlated with conversion of the cells from a nontumorigenic to a tumorigenic phenotype. The mechanisms by which oncogene-induced and spontaneous acquisition of factor independence occur are currently being investigated.
