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Involvement of c-Ski Oncoprotein in Carcinogenesis of Cholangiocacinoma Induced by Opisthorchis viverrini and N-nitrosodimethylamine

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Pathology & Oncology Research

Abstract

Opisthorchiasis is the major public health problem in the endemic areas of Thailand and Laos because Opisthorchis viverrini infection causes serious hepatobiliary diseases including CCA. The molecular mechanism of the CCA carcinogenesis induced by the infection remains obscure. To reveal the potential genes and signaling pathways to involve in the carcinogenesis, the present study investigated the expression of c-Ski, an oncogene, and two TGF-β signaling pathway relative genes, TGF-β and Smad4, during the development of CCA induced by O. viverrini infection in hamster model, and in human opisthorchiasis associated CCA. The results showed that the expression of c-Ski gene was greatly up-regulated during the carcinogenesis of CCA in hamster model. The overexpression of c-Ski was confirmed by immunohistological staining result which showed the increased expression of c-Ski protein in cytoplasm of the epithelial lining of hepatic bile ducts. Moreover, the immunohistological staining of the specimens of human opisthorchiasis associated CCA revealed the up-regulated expression of c-Ski and Smad4 proteins in the cytoplasm of the epithelial lining of hepatic bile ducts and stomal fibrosis respectively. The expression of TGF-β and Smad4 were up-regulated, which expression kinetics was time-dependent of CCA development. These results suggest that c-Ski is likely involved in the carcinogenesis of CCA induced by O. viverrini infection through regulating TGF-β signaling pathway.

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Abbreviations

CCA :

Choangiocarcinoma

TGF-β :

Transforming growth factor

NDMA:

N-nitrosodimethylamine

Smad4 :

SMAD family member 4

c-Ski :

Ski proto-oncogene

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Acknowledgments

This research was supported by the Research Strengthening Grant from National Center for Genetic Engineering and Biotechnology (BIOTEC), Graduate School of Medicine Facuty, Graduate School of Khon Kaen University, National Science and Technology Development Agency (NSTDA), Grant-in-Aid for Scientific Research (21590463) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Heiwa Nakajima Foundation which supported Dr. Thidarut Boonmars to stay in Gifu University Graduate School of Medicine in Japan for carrying out a part of experiments of the present research.

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Boonmars, T., Wu, Z., Boonjaruspinyo, S. et al. Involvement of c-Ski Oncoprotein in Carcinogenesis of Cholangiocacinoma Induced by Opisthorchis viverrini and N-nitrosodimethylamine. Pathol. Oncol. Res. 17, 219–227 (2011). https://doi.org/10.1007/s12253-010-9300-8

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  • DOI: https://doi.org/10.1007/s12253-010-9300-8

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