期刊
ONCOTARGET
卷 7, 期 52, 页码 87219-87231出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13529
关键词
osteopontin; EGFR; c-Jun; apoptosis; hepatocellular carcinoma
资金
- Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University
Previous clinical reports have found elevated osteopontin (OPN) levels in tumor tissues to be indicative of greater malignancy in human hepatocellular carcinoma (HCC). However, the role of OPN on carcinogenesis and its underlying mechanism remain unclear. In the present study, we investigated the oncogenic role of OPN in diethylnitrosamine (DEN)-induced hepatic carcinogenesis in mice. The overall incidence of hepatic tumors at 36 weeks was significantly lower in OPN knockout (KO) mice than in wild-type (WT) mice. Apoptosis was significantly enhanced in OPN KO mice, and was accompanied by the downregulation of epidermal growth factor receptor (EGFR). In the in vitro study, OPN suppression also led to lower mRNA and protein levels of EGFR associated with the downregulation of c-Jun in Hep3B and Huh7 human HCC cells lines, which resulted in increased apoptotic cell death in both cell lines. Moreover, a positive correlation was clearly identified between the expression of OPN and EGFR in human HCC tissues. These data demonstrate that the OPN deficiency reduced the incidence of chemically induced HCC by suppressing EGFR-mediated antiapoptotic signaling. An important implication of our findings is that OPN positively contributes to hepatic carcinogenesis.
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