Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants |
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Authors: | C Stocking C L?liger M Kawai S Suciu N Gough W Ostertag |
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Affiliation: | Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universit?t Hamburg, Federal Republic of Germany. |
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Abstract: | The factor-dependent myeloid precursor cell line D35 mutates spontaneously at a frequency greater than 2.4 x 10(-7) to growth factor autonomy. This frequency could be increased at least 20-fold by retrovirus insertional mutagenesis. The isolation and characterization of factor-independent mutants allowed the identification of genes involved in growth autonomy. Mutants could be subdivided into two sets: those that secreted a stimulating factor (10/11) and those that did not (1/11). In one case, the factor released was distinct from previously characterized growth factors. In most mutants (6/9), the activation of a growth factor gene was associated with rearrangement that could be attributed to the insertion of a transposable-like element either 5' or 3' of the factor coding region in all cases examined, excluding oncogene involvement. All factor-independent mutants were tumorigenic, consistent with the hypothesis that growth-factor independence initiated by aberrant growth factor gene activation is an important and early step in tumorigenesis. |
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