Nature and specificity of lymphokine independence induced by a selectable retroviral vector expressing v-src.
A murine retroviral vector, LSNLsrc, has been constructed and examined for its ability to induce growth factor independence in cells normally dependent on interleukin 2 (IL-2) or interleukin 3 (IL-3) for growth. The LSNLsrc vector coexpressed the v-src gene of Rous sarcoma virus and the neo gene from transposon Tn5, allowing infected cells to be selected on the basis of G418 resistance. The murine cell lines CTLL-2 and FD.C/1, which are dependent for growth on IL-2 and IL-3, respectively, were both readily infected with the LSNLsrc virus. LSNLsrc-infected, G418-resistant cultures of FD.C/1 cells were able to give rise to IL-3-independent progeny, but all G418-resistant CTLL-2 cells retained normal IL-2 dependence. The induction of IL-3 independence by v-src was not a direct event, since limiting dilution analysis of the LSNLsrc-infected FD.C/1 cells showed that most of them were IL-3 dependent, despite expression of v-src mRNA and active pp60v-src kinase. However, clones selected from this population in the presence of IL-3 were able to undergo a subsequent progression event and generate IL-3-independent progeny. The generation of factor-independent variants in the clonal cultures was a rare event, as witnessed by the death of most of the cells in each clone when IL-3 was withdrawn. Together, these data indicate that a secondary event, in addition to v-src expression, was required to generate IL-3-independent growth. No evidence was found for an autocrine mechanism of transformation involving IL-2, IL-3, interleukin 4, or granulocyte-macrophage colony-stimulating factor.
D002455:Cell Division; D002460:Cell Line; D005822:Genetic Vectors; D006133:Growth Substances / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology*; D015847:Interleukin-4; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation; D015688:Oncogene Protein pp60(v-src); D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D012191:Retroviridae Proteins / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*
D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D012191:Retroviridae Proteins; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)