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