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Title 

Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway

Authors 

Young-Ho ParkSun-Uk KimTae-Ho KwonJ M KimI S SongHye Jun ShinBo Kyoung LeeD H BangS J LeeD S LeeKyu Tae ChangBo Yeon KimDae Yeul Yu

Publisher 

Nature Publishing Group

Issue Date 

2016

Citation 

Oncogene, vol. 35, no. 27, pp. 3503-3513

Abstract 

The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras G12V -transformed HCC cells (H-ras G12V -HCC cells) and the tumor livers from H-ras G12V -transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras G12V -HCC cells and H-ras G12V -Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras G12V -HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras G12V -Tg livers. Consistent with this, knockdown of Prx II in H-ras G12V -HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras G12V -HCC cells and H-ras G12V -Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras G12V oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

ISSN 

0950-9232

Link 

http://dx.doi.org/10.1038/onc.2015.411

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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