title: Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen-activated protein kinase pathway.
abstract: Ameloblastoma is an epithelial benign tumor of the odontogenic apparatus and its growth mechanisms are not well understood. Fibroblast growth factor (FGF) 3, FGF7 and FGF10, which are expressed by the neural crest-derived ectomesenchymal cells, induce the proliferation of odontogenic epithelial cells during tooth development. Therefore, we examined the expression and function of these FGFs in ameloblastoma. We examined 32 cases of ameloblastoma as well as AM-1 cells (an ameloblastoma cell line) and studied the expression of FGF3, FGF7, FGF10 and their specific receptors, namely, FGF receptor (FGFR) 1 and FGFR2. Proliferation, mitogen-activated protein kinase (MAPK) signaling and PI3K signaling were examined in AM-1 cells after the addition of FGF7, FGF10 and these neutralizing antibodies. The expression of FGF7, FGF10, FGFR1 and FGFR2 was detected in ameloblastoma cells and AM-1 cells, while that of FGF3 was not. FGF7 and FGF10 stimulated AM-1 cell proliferation and phosphorylation of p44/42 MAPK. However, Akt was not phosphorylated. Blocking the p44/42 MAPK pathway by using a specific mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor (U0126) completely neutralized the effects of FGF7 and FGF10 on AM-1 cell proliferation. However, Anti FGF7 and FGF10 neutralizing antibodies did not decrease cell proliferation and MAPK phosphorylation of AM-1 cells. These results suggested that FGF7 and FGF10 are involved in the proliferation of ameloblastoma cells through the MAPK pathway.
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mitsuyasu
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kawano
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nakamura
authors.forename: Shiori
authors.initials: S
authors.lastname: Kanda
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000564:Ameloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007573:Jaw Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: C496463:FGF10 protein, human; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3