title: Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma.
abstract: Opisthorchiasis has the significant relationship with the high prevalence of cholangiocarcinoma (CCA; a bile duct cancer) in the endemic areas in Southeast Asia. To reveal the molecular mechanism of the tumorigenesis induced by Opisthorchis viverrini infection, the present study investigated the kinetic expression of RB pathway genes, including RB1, p16(INK4), cyclin D1, and CDK4, during the development of opisthorchiasis-associated CCA in hamster model. The results of quantitative real-time polymerase chain reaction indicated that the expressions of RB1 and p16(INK4) were down-regulated during the development of CCA induced by infection plus N-nitrosodimethylamine treatment in a time-dependent manner. On the other hand, the expressions of cyclin D1 and CDK4 were up-regulated. The expression kinetics was corresponding to the pathological progression of the opisthorchiasis-associated CCA, revealed by histopathological observation. Moreover, the analysis of the expression of these genes in human opisthorchiasis-associated CCA cases showed the decreased expression of RB1 and p16(INK4) in 50% and 82.7% cases and overexpression of cyclin D1 and CDK4 in half cases, respectively. The results suggested that RB pathway is likely involved in the tumorigenesis of opisthorchiasis-induced CCA and proposed the potential application of some of these genes as biomarkers in predispose and molecular therapy of the parasite-associated cancer.
authors: Department of Parasitology, Khon Kaen University, Khon Kaen 40002, Thailand.
authors: Thidarut
authors: T
authors: Boonmars
authors: Zhiliang
authors: Z
authors: Wu
authors: Sirintip
authors: S
authors: Boonjaruspinyo
authors: Somchai
authors: S
authors: Pinlaor
authors: Isao
authors: I
authors: Nagano
authors: Yuzo
authors: Y
authors: Takahashi
authors: Butsara
authors: B
authors: Kaewsamut
authors: Puangrat
authors: P
authors: Yongvanit
mesh_terms: D000818:Animals; D018281:Cholangiocarcinoma / Q000469:parasitology / Q000473:pathology*; D003003:Clonorchiasis / Q000150:complications* / Q000469:parasitology / Q000473:pathology*; D006224:Cricetinae; D019938:Cyclin D1 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009891:Opisthorchis / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4