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Updated: Jun 19, 2026
Induction and Testing of Hypoxia in Cell Culture
Published on: August 12, 2011
Suppression of tumor growth through disruption of hypoxia-inducible transcription
1The Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115,USA.
Abstract:
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.
Insights
Targeting tumor hypoxia offers a novel therapeutic strategy. Disrupting the interaction between hypoxia-inducible factor and transcriptional coactivators inhibits tumor growth by blocking hypoxia-induced gene expression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Chronic tumor hypoxia is linked to increased angiogenesis and tumor progression.
- Current therapies target hypoxic tumor cells or use hypoxia-activated drugs.
- A new strategy involves disrupting the normal transcriptional response to hypoxia.
Purpose of the Study:
- To investigate a novel therapeutic approach by selectively disrupting the transcriptional response to hypoxia.
- To determine if blocking specific coactivator interactions can inhibit tumor growth.
Main Methods:
- Focusing on the blockade of hypoxia-inducible factor (HIF) interaction with the CH1 domain of p300 and CREB binding protein (CBP).
- Evaluating the impact of this blockade on hypoxia-inducible gene expression.
- Assessing the effect on tumor growth in relevant models.
Main Results:
- Specific blockade of the HIF-CH1 interaction with p300/CBP attenuates hypoxia-inducible gene expression.
- This disruption leads to a significant diminution of tumor growth.
- The findings suggest a new therapeutic avenue targeting transcriptional coactivation in tumors.
Conclusions:
- Disrupting the normal co-activational response to hypoxia represents a promising therapeutic strategy.
- Targeting the HIF-CH1-coactivator interaction offers a novel method for cancer treatment.
- This approach may overcome limitations of current hypoxia-targeted therapies.
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