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Altered gene expression in Opisthorchis viverrini ‐associated cholangiocarcinoma in hamster model
Author(s) -
Loilome Watcharin,
Yongvanit Puangrat,
Wongkham Chaisiri,
Tepsiri Nisana,
Sripa Banchob,
Sithithaworn Paiboon,
Hanai Shuji,
Miwa Masanao
Publication year - 2006
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20094
Subject(s) - biology , opisthorchis viverrini , downregulation and upregulation , carcinogenesis , microbiology and biotechnology , clonorchis sinensis , cancer research , gene expression , gene , liver fluke , genetics , immunology , helminths
Cholangiocarcinoma (CCA) induced by liver fluke ( Opisthorchis viverrini , Ov) infection is one of the most common and serious disease in northeast Thailand. To elucidate the molecular mechanism of cholangiocarcinogenesis induced by Ov infection, we employed a hamster model of CCA induced by Ov and N ‐nitrosodimethylamine and analyzed candidate genes involved in CCA using fluorescence differential display‐PCR. Of 149 differentially amplified bands we identified, the upregulation of 23 transcripts and downregulation of 1 transcript related to CCA hamsters were confirmed by a reverse northern macroarray blot. The upregulated genes include signal transduction protein kinase A regulatory subunit Iα ( Prkar1a ), myristoylated alanine‐rich protein kinase C substrate, transcriptional factor LIM‐4‐only domain, oxysterol‐binding protein involved in lipid metabolism, splicing regulatory protein 9, ubiquitin conjugating enzyme involved in protein degradation, β tubulin, β actin, and collagen type VI. Quantitative real‐time PCR confirmed that the expression of Prkar1a was significantly higher in CCA and its precursor lesion when compared with normal liver and normal gall bladder epithelia ( P < 0.05). Prkar1a expression tended to increase along with the progression of biliary transformation from hyperplasia and precancerous lesions to carcinoma. These findings contribute to our understanding of the processes involved in the molecular carcinogenesis of CCA in order to provide a unique perspective on the development of new chemotherapeutics in future. © 2006 Wiley‐Liss, Inc.