Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
Through a genome-wide cDNA microarray, we identified that the paternally expressed gene 10 (PEG10) was highly expressed in a great majority of hepatocellular carcinomas, although its expression was absent in normal liver cells. Exogenous expression of PEG10 conferred oncogenic activity and transfection of hepatoma cells with antisense S-oligonucleotides suppressing PEG10 resulted in their growth inhibition. Additional experiments revealed that PEG10 protein associated with SIAH1, a mediator of apoptosis, and that overexpression of PEG10 decreased the cell death mediated by SIAH1. These findings suggested that development of drug(s) inhibiting PEG10 activity could be a novel approach for the treatment of hepatocellular carcinomas.
Okabe
Hiroshi
H
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Satoh
Seiji
S
Furukawa
Yoichi
Y
Kato
Tatsushi
T
Hasegawa
Suguru
S
Nakajima
Yumi
Y
Yamaoka
Yoshio
Y
Nakamura
Yusuke
Y
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D025941:Protein Interaction Mapping; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins