Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice.
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.
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Jianfeng
J
Jin
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Dayong
D
Wang
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Haifeng
H
Xiao
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Huiyan
H
Wei
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
Cedric
C
Matunda
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
He
H
Zhang
Department of Respiratory Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
Xin
X
Li
Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medicine Sciences, Harbin, China.
Chuxuan
C
Wang
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medicine Sciences, Harbin, China.
Chaoxia
C
Zou
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medicine Sciences, Harbin, China.
Xu
X
Gao
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China. Electronic address: zhaowm@ems.hrbmu.edu.cn.
Weiming
W
Zhao
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China; Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: lq_79224@163.com.
Qiang
Q
Li
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002273:Carcinogens; D004052:Diethylnitrosamine; D051547:Heme Oxygenase-1 / Q000235:genetics*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D002273:Carcinogens; D008565:Membrane Proteins; D004052:Diethylnitrosamine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
Diethylnitrosamine; Heme oxygenase-1; Liver tumorigenesis; Transgenic animal