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Suppression of tumor growth through
disruption of hypoxia-inducible transcription
Andrew L. Kung, Stream Wang, Jeffery M. Klco, William G. Kaelin & David
M. Livingston
The
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street,
Boston, Massachusetts 02115,USA
Correspondence should be addressed to D M Livingston. e-mail: david_livingston@dfci.harvard.edu
Chronic
hypoxia, a hallmark of many tumors, is associated with angiogenesis and tumor
progression.
Strategies
to treat tumors have been developed in which tumor cells are targeted with drugs
or gene-therapy vectors specifically activated under hypoxic conditions.
Here
we report a different approach, in which the normal transcriptional response to
hypoxia is selectively disrupted.
Our
data indicate that specific blockade of the interaction of hypoxia-inducible
factor with the CH1 domain of its p300 and CREB binding protein transcriptional
coactivators leads to attenuation of hypoxia-inducible gene expression and
diminution of tumor growth.
Thus,
disrupting the normal co-activational response to hypoxia may be a new and
useful therapeutic strategy.
(c)
2000 Nature Publishing Group
Source:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v6/n12/abs/nm1200_1335.html&dynoptions=doi1092821596
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