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Activation of HIF-1? does not increase intestinal tumorigenesis.


ABSTRACT: The hypoxic response is mediated by two transcription factors, hypoxia-inducible factor (HIF)-1? and HIF-2?. These highly homologous transcription factors are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell proliferation, and cell survival. HIF-1? and HIF-2? are activated early in cancer progression and are important in several aspects of tumor biology. HIF-1? and HIF-2? have overlapping and distinct functions. In the intestine, activation of HIF-2? increases inflammation and colon carcinogenesis in mouse models. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1? is beneficial and can reduce intestinal inflammation. HIF-1? is a critical transcription factor regulating epithelial barrier function following inflammation. The beneficial value of pharmacological agents that chronically activate HIF-1? is decreased due to the tumorigenic potential of HIFs. The present study tested the hypothesis that chronic activation of HIF-1? may enhance colon tumorigenesis. Two models of colon cancer were assessed, a sporadic and a colitis-associated colon cancer model. Activation of HIF-1? in intestinal epithelial cells does not increase carcinogenesis or progression of colon cancer. Together, the data provide proof of principle that pharmacological activation of HIF-1? could be a safe therapeutic strategy for inflammatory bowel disease.

SUBMITTER: Xue X 

PROVIDER: S-EPMC4101679 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Activation of HIF-1α does not increase intestinal tumorigenesis.

Xue Xiang X   Ramakrishnan Sadeesh K SK   Shah Yatrik M YM  

American journal of physiology. Gastrointestinal and liver physiology 20140529 2


The hypoxic response is mediated by two transcription factors, hypoxia-inducible factor (HIF)-1α and HIF-2α. These highly homologous transcription factors are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell proliferation, and cell survival. HIF-1α and HIF-2α are activated early in cancer progression and are important in several aspects of tumor biology. HIF-1α and HIF-2α have overlapping and distinct functions. In the intestine, activation of HIF-2α increases inflammatio  ...[more]

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