Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model.
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 Ialpha (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, beta tubulin, beta 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.
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Watcharin
W
Loilome
Puangrat
P
Yongvanit
Chaisiri
C
Wongkham
Nisana
N
Tepsiri
Banchob
B
Sripa
Paiboon
P
Sithithaworn
Shuji
S
Hanai
Masanao
M
Miwa
D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000469:parasitology; D001653:Bile Ducts, Intrahepatic; D015152:Blotting, Northern; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000469:parasitology; D006224:Cricetinae; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008647:Mesocricetus; D009363:Neoplasm Proteins / Q000235:genetics*; D009602:Nitrosamines / Q000633:toxicity; D009889:Opisthorchiasis / Q000235:genetics* / Q000469:parasitology; D009891:Opisthorchis / Q000472:pathogenicity*
D009363:Neoplasm Proteins; D009602:Nitrosamines; D004128:Dimethylnitrosamine