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Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 2118-2125
STAT5 activation contributes to growth and viability in
Bcr/Abl-transformed cells
Christian Sillaber,
Franck Gesbert,
David A. Frank,
Martin Sattler, and
James D. Griffin
From the Department of Adult Oncology, Dana Farber Cancer Institute,
Harvard Medical School, Boston, MA.
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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