| First Author | Xue X | Year | 2014 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 307 |
| Issue | 2 | Pages | G187-95 |
| PubMed ID | 24875099 | Mgi Jnum | J:221716 |
| Mgi Id | MGI:5641409 | Doi | 10.1152/ajpgi.00112.2014 |
| Citation | Xue X, et al. (2014) Activation of HIF-1alpha does not increase intestinal tumorigenesis. Am J Physiol Gastrointest Liver Physiol 307(2):G187-95 |
| abstractText | The hypoxic response is mediated by two transcription factors, hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha. These highly homologous transcription factors are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell proliferation, and cell survival. HIF-1alpha and HIF-2alpha are activated early in cancer progression and are important in several aspects of tumor biology. HIF-1alpha and HIF-2alpha have overlapping and distinct functions. In the intestine, activation of HIF-2alpha increases inflammation and colon carcinogenesis in mouse models. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1alpha is beneficial and can reduce intestinal inflammation. HIF-1alpha is a critical transcription factor regulating epithelial barrier function following inflammation. The beneficial value of pharmacological agents that chronically activate HIF-1alpha is decreased due to the tumorigenic potential of HIFs. The present study tested the hypothesis that chronic activation of HIF-1alpha may enhance colon tumorigenesis. Two models of colon cancer were assessed, a sporadic and a colitis-associated colon cancer model. Activation of HIF-1alpha 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-1alpha could be a safe therapeutic strategy for inflammatory bowel disease. |
