Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants.
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.
Stocking
C
C
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Federal Republic of Germany.
Löliger
C
C
Kawai
M
M
Suciu
S
S
Gough
N
N
Ostertag
W
W
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002461:Cell Line, Transformed; D003115:Colony-Stimulating Factors / Q000235:genetics; D004247:DNA / Q000032:analysis; D004251:DNA Transposable Elements; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D003115:Colony-Stimulating Factors; D004251:DNA Transposable Elements; D006133:Growth Substances; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA