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Overexpression of PU.1 Induces Growth and Differentiation Inhibition and Apoptotic Cell Death in Murine Erythroleukemia Cells

Yamada, Toshiyuki, Kondoh, Nobuo, Matsumoto, Mana, Yoshida, Midori, Maekawa, Akihiko, Oikawa, Tsuneyuki·1997·Blood
DOI 10.1182/blood.v89.4.1383
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Abstract

PU.1 is a member of the ets family of transcription factors and is expressed in Friend virus-induced murine erythroleukemia (MEL) cells as a consequence of proviral integration into the PU.1/Spi-1 locus. After induction of MEL cell differentiation by treatment with dimethylsulfoxide (DMSO), expression of the PU.1/Spi-1 gene decreased before induction of β-globin gene expression. Overexpression of PU.1 by using a zinc-inducible expression plasmid in MEL cells resulted in unexpected growth inhibition of the transfectants. When PU.1-overexpressing transfectants were treated with DMSO, growth inhibition became much pronounced and apoptosis was induced. Expression of the β-globin gene was not induced under this condition. Neither growth inhibition nor apoptosis was induced in MEL cells after expression of mutant PU.1 proteins with a deletion of the activation domain or the DNA-binding Ets domain irrespective of the presence of DMSO. Interestingly, β-globin gene expression was not induced in the transfectants expressing the former mutant, whereas it was induced in those expressing the latter one in the presence of DMSO. These results indicate that overexpression of PU.1 in MEL cells results in growth and differentiation inhibition and, in conjunction with DMSO treatment, apoptotic cell death. These results also suggest that the activation domain and the Ets domain of PU.1 contribute differently to induction of these effects.

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Citations

Cites

Research works printed but not linked: 25

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Metadata

Authors
Yamada, T., Kondoh, N., Matsumoto, M., Yoshida, M., Maekawa, A., & Oikawa, T.
Venue
Blood
Publisher
American Society of Hematology
Published
1997-02-15
Volume
89
Issue
4
Pages
1383-1393
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood.v89.4.1383
Cited by
87
References
10
Language
en

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