Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants

Cell. 1988 Jun 17;53(6):869-79. doi: 10.1016/s0092-8674(88)90329-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division
  • Cell Line, Transformed
  • Colony-Stimulating Factors / genetics
  • DNA / analysis
  • DNA Transposable Elements
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Growth Substances / biosynthesis
  • Growth Substances / genetics*
  • Hematopoietic Stem Cells / cytology*
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Hybridization
  • Oncogenes*
  • RNA, Messenger / analysis
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic

Substances

  • Colony-Stimulating Factors
  • DNA Transposable Elements
  • Growth Substances
  • RNA, Messenger
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • DNA

Associated data

  • GENBANK/M21200