Deregulated expression of the PU.1 transcription factor blocks murine erythroleukemia cell terminal differentiation

Oncogene. 1997 Jan 9;14(1):123-31. doi: 10.1038/sj.onc.1200807.


Murine erythroleukemia (MEL) cells are transformed erythroid precursors that are blocked from completing the late stages of erythroid differentiation. A frequent event in the generation of these malignant cells is deregulation of the hematopoietic-specific transcription factor PU.1 (Spi-1) by retroviral insertion of the spleen-focus-forming virus component of Friend virus. During chemically induced reinitiation of MEL cell terminal differentiation, expression of PU.1 is rapidly down-regulated, suggesting that PU.1 might interfere with processes required for terminal differentiation of erythroid precursors. To investigate the role of PU.1 in erythroid differentiation we transfected MEL cells with a PU.1 cDNA controlled by the eucaryotic translation elongation factor EF1 alpha promoter. Deregulated expression of PU.1 blocked chemically induced differentiation and terminal cell division. Deregulated expression of two other protooncogenes, c-myc and c-myb, also has been shown to block MEL differentiation. We present evidence that PU.1 inhibits terminal differentiation at an earlier step than c-Myc and c-Myb. Thus reinitiation of MEL cell terminal differentiation appears to be controlled by an ordered program of turning off several protooncogenes. Down-regulation of PU.1 may be a very early step in this program.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Friend murine leukemia virus*
  • Gene Expression Regulation
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / metabolism
  • Leukemia, Erythroblastic, Acute / pathology*
  • Leukemia, Erythroblastic, Acute / virology
  • Mice
  • Protein Biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Trans-Activators*
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Trans-Activators
  • proto-oncogene protein Spi-1