title: Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.
abstract: To disclose molecular mechanisms of cholangiocarcinogenesis and to search for novel diagnostic markers and therapeutic targets for cholangiocarcinoma, we previously analyzed gene-expression profiles of 25 intrahepatic cholangiocarcinomas (ICCs) by means of a cDNA microarray re-presenting 27,648 genes. Among the genes frequently up-regulated in the cancer cells, we focused on PSF2 (partner of SLD five 2), a component of the GINS multiprotein complex that plays a crucial role in initiation of DNA replication. Semi-quantitative RT-PCR analysis of clinical samples confirmed high levels of PSF2 expression in the cancer cells, but expression of this gene was barely detectable in normal vital organs. Transfection of ETK-1 and HuH28 cells with short-interfering RNA specific to PSF2 reduced the amount of transcript and suppressed cell growth, suggesting that PSF2 may play an important role in development of cholangio-carcinoma. The findings reported here provide new insights into human cholangiocarcinogenesis and may contribute to the development of novel therapeutic drugs for this type of liver cancer.
authors.affiliation: Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Obama
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Ura
authors.forename: Seiji
authors.initials: S
authors.lastname: Satoh
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C073119:TAP1 protein, human; C071692:TAP2 protein, human