Distinct Classes of Factor-Independent Mutants can be Isolated after Retroviral Mutagenesis of a Human Myeloid Stem Cell Line
| Autor: | Karl Klingler, Atsushi Miyajima, Carol Stocking, Thomas Wagener, Christian Starke, Jutta Friel, Wolfram Ostertag, Ulla Bergholz, Toshio Kitamura |
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| Rok vydání: | 1993 |
| Předmět: |
Virus Integration
medicine.medical_treatment Genetic Vectors Clinical Biochemistry Mutant Mutagenesis (molecular biology technique) Biology Cell Line Tissue culture Endocrinology Myeloid stem cell medicine Humans Mutation frequency Growth Substances Autocrine signalling Growth factor Cell Biology Hematopoietic Stem Cells Phenotype Molecular biology Receptors Interleukin-3 Mutagenesis Insertional Retroviridae Receptors Granulocyte-Macrophage Colony-Stimulating Factor Mutation DNA Transposable Elements |
| Zdroj: | Growth Factors. 8:197-209 |
| ISSN: | 1029-2292 0897-7194 |
| DOI: | 10.3109/08977199309011023 |
| Popis: | Retroviral insertion mutagenesis has been used extensively in vivo but not in vitro to induce and identify critical mutations during oncogenic progression and differentiation. We have developed a tissue culture system using the human, growth factor-dependent, hematopoietic precursor cell line TF-1 that permits the use of retroviral vectors to induce a large (up to 28-fold) increase in the mutation frequency to growth factor independence and thus the isolation of many mutants. The mutation frequency, as expected, is directly proportional to the number of retroviral insertions (2.2 x 10(-7) mutants per insertion). The mutant phenotypes can be subdivided into mutants that release growth factors and those that do not ("autonomous" mutants). The majority of growth factor-producing mutants release an unidentified ligand. A subset of the autonomous mutants shows alterations in expression of the alpha subunit of either the GM-CSF or the IL-3 receptor. One mutant expresses neither GM-CSF nor IL-3 alpha receptor chains, thus showing coordinate regulation of the alpha receptor subunits. |
| Databáze: | OpenAIRE |
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