Abstract
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 EF1α 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.
Original language | English (US) |
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Pages (from-to) | 123-131 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 14 |
Issue number | 1 |
DOIs | |
State | Published - 1997 |
Keywords
- Differentiation
- MEL cells
- PU.1
- Spi-1
- c-myb
- c-myc
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research