Up-regulation of PSF2, a member of the GINS multiprotein complex, in intrahepatic cholangiocarcinoma.
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.
Obama
Kazutaka
K
Laboratory of Molecular Medicine, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Ura
Katsuaki
K
Satoh
Seiji
S
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
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
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