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Publication : Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice.

First Author  Jin J Year  2016
Journal  Biochem Biophys Res Commun Volume  481
Issue  1-2 Pages  169-175
PubMed ID  27810363 Mgi Jnum  J:240891
Mgi Id  MGI:5896696 Doi  10.1016/j.bbrc.2016.10.148
Citation  Jin J, et al. (2016) Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice. Biochem Biophys Res Commun 481(1-2):169-175
abstractText  Heme oxygenase (HO) is the rate-limiting enzyme in heme metabolism. HO-1 exhibits anti-oxidative and anti-inflammatory function via the actions of its metabolite, respectively. A growing body of evidence demonstrates that HO-1 is implicated in the pathogenesis and progression of several types of cancer. However, whether HO-1 takes part in healthy-premalignant-malignant transformation is still undefined. In this study, we took advantage of transgenic mice which over-expressed HO-1 dominant negative mutant (HO-1 G143H) and observed its susceptibility to DEN-induced hepatocarcinogenesis. Our results indicate that HO-1 G143H mutant accelerates the progression of tumorigenesis and tumor growth. The mechanism is closely related to enhancement of ROS production which induce more hepatocytes death and secretion of inflammatory cytokines, proliferation of surviving hepatocytes. Our result provides the direct evidence that HO-1 plays an important protective role in liver carcinogenesis. Alternatively, we suggest the possible explanation on effect of HO-1 promoter polymorphism which involved in tumorigenesis.
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