title: The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer.
abstract: POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.
authors.affiliation: 1] Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan [2] Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Arao
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: De Velasco
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Department of Pathology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D011544:Pseudogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger