Inactivation of a c-Myb/estrogen receptor fusion protein in transformed primary cells leads to granulocyte/macrophage differentiation and down regulation of c-kit but not c-myc cdc2

Annette Hogg, Sabine Schirm, Hideki Nakagoshi, Paul Bartley, Shunsuke Ishii, J. Michael Bishop, Thomas J. Gonda

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Primary murine fetal hemopoietic cells were transformed with a fusion protein consisting of the ligand-binding domain of the estrogen receptor and a carboxyl-terminally truncated c-Myb protein (ERMYB). The ERMYB-transformed hemopoietic cells exhibit an immature myeloid phenotype when grown in the presence of β-estradiol. Upon removal of β-estradiol, the ERMYB cells display increased adherence, decreased clonogenicity and differentiate to cells exhibiting granulocyte or macrophage morphology. The expression of the c-myc, c-kit, cdc2 and bcl-2 genes, which are putatively regulated by Myb, was investigated in ERMYB cells grown in the presence or absence of β-estradiol. Neither c-myc nor cdc2 expression was down-regulated after removal of β-estradiol demonstrating that differentiation is not a consequence of decreased transactivation of these genes by ERMYB. While bcl-2 expression was reduced by 50% in ERMYB cells grown in the absence of β-estradiol, there was no increase in DNA laddering, suggesting that Myb was not protecting ERMYB cells from apoptosis. In contrast, a substantial (200-fold) decrease in c-kit mRNA level was observed following differentiation of ERMYB cells, and c-kit mRNA could be partially re-induced by the re-addition of β-estradiol. Furthermore, a reporter construct containing the c-kit promoter was activated when cotransfected with a Myb expression vector, providing further evidence of a role for Myb in the regulation of c-kit.

Original languageEnglish
Pages (from-to)2885-2898
Number of pages14
Issue number24
Publication statusPublished - Jan 1 1997
Externally publishedYes



  • Apoptosis
  • Apoptosis target genes
  • Bcl-2
  • Differentiation
  • Myb

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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