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Induction and Testing of Hypoxia in Cell Culture
Published on: August 12, 2011
Suppression of dual-specificity phosphatase-2 by hypoxia increases chemoresistance and malignancy in human cancer
Shih-Chieh Lin1, Chun-Wei Chien, Jenq-Chang Lee
1Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
The Journal of Clinical Investigation
|April 15, 2011
Summary
Hypoxia inducible factor-1 (HIF-1) suppresses DUSP2, promoting tumor growth and chemoresistance. Restoring DUSP2 inhibits tumor progression and resensitizes tumors to chemotherapy, offering a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hypoxia inducible factor-1 (HIF-1) is a key regulator of cellular response to low oxygen.
- HIF-1α is elevated in many tumors, driving progression and chemoresistance.
- The link between HIF-1 and chemoresistance is not fully understood.
Purpose of the Study:
- To investigate the role of dual-specificity phosphatase-2 (DUSP2) in HIF-1-mediated tumor progression and chemoresistance.
- To explore DUSP2 as a potential therapeutic target for chemoresistant cancers.
Main Methods:
- Analysis of DUSP2 expression in human cancers and correlation with HIF-1α levels and malignancy.
- Inhibition and forced expression of DUSP2 in human cancer cell lines and xenograft mouse models.
- Assessment of gene expression related to drug response, angiogenesis, cell survival, and apoptosis.
Main Results:
- DUSP2 expression is reduced in many cancers and inversely correlates with HIF-1α and malignancy.
- HIF-1α inhibits DUSP2 transcription, leading to prolonged ERK phosphorylation and increased chemoresistance.
- DUSP2 reexpression reduced tumor growth and increased drug sensitivity in vivo.
- DUSP2 downregulates genes involved in drug response, angiogenesis, cell survival, and apoptosis.
Conclusions:
- DUSP2 is a critical downstream target of HIF-1, regulating tumor progression and chemoresistance.
- DUSP2 represents a potential novel therapeutic target for chemoresistant tumors.
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