RRC ID 61920
Author Baba T, Sakamoto Y, Kasamatsu A, Minakawa Y, Yokota S, Higo M, Yokoe H, Ogawara K, Shiiba M, Tanzawa H, Uzawa K.
Title Persephin: A potential key component in human oral cancer progression through the RET receptor tyrosine kinase-mitogen-activated protein kinase signaling pathway.
Journal Mol Carcinog
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.
Volume 54(8)
Pages 608-17
Published 2015-8-1
DOI 10.1002/mc.22127
PMID 24375483
MeSH Adult Aged Aged, 80 and over Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Cycle Checkpoints Cell Line, Tumor Disease Progression Humans MAP Kinase Signaling System* Middle Aged Mouth Neoplasms / genetics Mouth Neoplasms / metabolism Mouth Neoplasms / pathology* Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism* Receptor Protein-Tyrosine Kinases / metabolism Up-Regulation
IF 3.825
Human and Animal Cells Ca9-22(RCB1976) Sa3(RCB0980) HSC-2(RCB1945) HSC-4(RCB1902)