title: TNFalpha played a role in induction of Akt and MAPK signals in ameloblastoma.
abstract: Tumour necrosis factor alpha (TNFalpha) is known crucial in inducing cell survival, proliferation, differentiation, and apoptosis. In the present study, we found that TNFalpha as well as its receptors, TNFR1 (TNF Receptor 1) and TNFR2, were clearly expressed in ameloblastoma tissues and AM-1 cells. By stimulation of TNFalpha in AM-1 cells, the phosphorylation of Akt (Ser473) and p44/42 mitogen-activated protein kinase (MAPK) (Thr202/Tyr204) was markedly increased in TNFalpha concentration and time dependent manner. Pretreatment with U0126, mitogen-activated extracellular-regulated kinase (MEK) 1/2 inhibitor, prior to TNFalpha stimulation, specifically inhibited TNFalpha-induced phosphorylation of p44/42 MAPK (Thr202/Tyr204) in AM-1 cells. Meanwhile, pretreatment with LY294002, phosphatidylinositol-3-OH kinase (PI3K) inhibitor, could inhibit both TNFalpha-induced phosphorylation of Akt (Ser473) and p44/42 MAPK (Thr202/Tyr204). These results suggested that TNFalpha is expressed in ameloblastoma and it can induce Akt and p44/42 MAPK activation through PI3K, which later might induce cell survival and proliferation in ameloblastoma.
authors.affiliation: Section of Oral and Maxillofacial Oncology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Laifa
authors.initials: L
authors.lastname: Hendarmin
authors.forename: Ferry
authors.initials: F
authors.lastname: Sandra
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakao
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ohishi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000564:Ameloblastoma / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007124:Immunoenzyme Techniques; D007573:Jaw Neoplasms / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
chemical_list: D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C494918:AKT1 protein, human