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

Govinda Rao, Natasha Rekhtman, Genhong Cheng, Tatiana Krasikov, Arthur I. Skoultchi

Research output: Contribution to journalArticle

86 Scopus citations

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 languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalOncogene
Volume14
Issue number1
DOIs
StatePublished - Jan 1 1997

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Keywords

  • Differentiation
  • MEL cells
  • PU.1
  • Spi-1
  • c-myb
  • c-myc

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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