title: Persephin: A potential key component in human oral cancer progression through the RET receptor tyrosine kinase-mitogen-activated protein kinase signaling pathway.
abstract: Persephin (PSPN) is a neurotrophic factor of the glial cell line-derived neurotrophic factor (GDNF) family that promotes survival of multiple populations of neurons. Little is known about the relevance of PSPN in human malignancy including oral squamous cell carcinoma (OSCC). This study was undertaken to evaluate PSPN mRNA and protein expression by analyzing cellular proliferation and the cell cycle in PSPN knockdown cells in vitro. PSPN mRNA and protein were significantly (P < 0.05) up-regulated in OSCC-derived cells compared with human normal oral keratinocytes (n = 7). Cellular proliferation decreased significantly (P < 0.05) in PSPN knockdown cells with reduced receptor tyrosine kinase (RTK) signaling, and cell-cycle arrest at the G1 phase resulted from up-regulation of the cyclin-dependent kinase inhibitors (p21(Cip1) , p27(Kip1) , p15(INK4B) , and p16(INK4A) ). Furthermore, the PSPN protein expression in 101 primary OSCCs was significantly (P < 0.05) higher than in normal counterparts. Among the clinical variables analyzed, overexpression of PSPN also was related closely (P < 0.05) to tumoral size. Our results suggested that PSPN is a possible key regulator of OSCC progression via PSPN-RET-mitogen-activated protein kinase activation and that PSPN overexpression may have diagnostic potential for OSCC.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Minakawa
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higo
authors.affiliation: Department of Oral and Maxillofacial Surgery Research Institute, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.affiliation: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.affiliation: Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Dentistry-Oral and Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009419:Nerve Tissue Proteins; C110758:persephin; D020794:Receptor Protein-Tyrosine Kinases
keywords: cell-cycle arrest; cyclin-dependent kinase inhibitors; oral squamous cell carcinoma; persephin; proliferation