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STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells

Sillaber, Christian, Gesbert, Franck, Frank, David A., Sattler, Martin, Griffin, James D.·2000·Blood
DOI 10.1182/blood.v95.6.2118
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Abstract

The transcription factor STAT5 is constitutively tyrosine phosphorylated and activated after transformation of hematopoietic cells by p210Bcr/Abl. A truncated form of STAT5B (▵STAT5; aa, 1-683) that lacks tyrosine 699 and the transcriptional activation domain was introduced into Ba/F3p210 cells under the control of a tetracycline-inducible promoter. Treatment of these cells with doxycycline, a tetracycline analogue, induced expression of ▵STAT5 and inhibited STAT5-dependent transcription. ▵STAT5 coprecipitated with STAT5 and decreased Bcr/Abl-dependent tyrosine phosphorylation of endogenous STAT5. Induction of ▵STAT5 inhibited growth of Ba/F3p210 cells (26%-52% of control levels at 4 days) but did not cause cell-cycle arrest. ▵STAT5 reduced viability of Ba/F3p210 cells and increased sensitivity of the cells to the cytotoxic drugs hydroxyurea and cytarabine. These results indicate that high-level expression of ▵STAT5, as achieved here by using a tetracycline-inducible promoter, inhibits STAT5 activity, reduces the growth rate of Ba/F3p210 cells by inhibiting viability, and results in increased sensitivity to chemotherapeutic drugs. It is therefore likely that STAT5 activation plays a role in the transformation of hematopoietic cell lines by p210Bcr/Abl.

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Metadata

Authors
Sillaber, C., Gesbert, F., Frank, D. A., Sattler, M., & Griffin, J. D.
Affiliations
From the Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA.
Venue
Blood
Publisher
American Society of Hematology
Published
2000-03-15
Volume
95
Issue
6
Pages
2118-2125
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood.v95.6.2118
Cited by
198
References
0
Language
en

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CoChat. (2026). Citation check: STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. https://app.cochat.ai/papers/10.1182/blood.v95.6.2118
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Sillaber, C., Gesbert, F., Frank, D. A., Sattler, M., & Griffin, J. D. (2000). STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. Blood. https://doi.org/10.1182/blood.v95.6.2118