Nature and specificity of lymphokine independence induced by a selectable retroviral vector expressing v-src
| Autor: | D Cosman, R W Overell, K E Weisser, B Gallis, J D Watson, M B Widmer |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Interleukin 2
Genetic Vectors Retroviridae Proteins Lymphocyte Activation Cell Line Oncogene Protein pp60(v-src) Viral vector medicine Growth Substances Molecular Biology Interleukin 4 Interleukin 3 Rous sarcoma virus biology Interleukins Lymphokine Interleukin Oncogenes Cell Biology Protein-Tyrosine Kinases biology.organism_classification Virology Molecular biology Retroviridae v-Src Interleukin-2 Interleukin-3 Interleukin-4 Cell Division Research Article T-Lymphocytes Cytotoxic medicine.drug |
| Zdroj: | Molecular and Cellular Biology. 7:3394-3401 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.7.10.3394 |
| Popis: | 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in the clonal cultures was a rare event, as witnessed by the death of most of the cells in each clone when IL-3 was withdrawn.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. |
| Databáze: | OpenAIRE |
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