TNFα played a role in induction of Akt and MAPK signals in ameloblastoma

Tumour necrosis factor alpha (TNF alpha) is known crucial in inducing cell survival, proliferation, differentiation, and apoptosis. In the present study, we found that TNFa as well as its receptors, TNFR1 (TNF Receptor 1) and TNFR2, were clearly expressed in ameloblastoma tissues and AM-1 cells. By stimulation of TNFa in AM-1 cells, the phosphorylation of Akt (Ser473) and p44/42 mitogen-activated protein kinase (MAPK) (Thr202/Tyr204) was markedly increased in TNF alpha concentration and time dependent manner. Pretreatment with 00126, mitogen-activated extracellular-regulated kinase (MEK) 1/2 inhibitor, prior to TNFa stimulation, specifically inhibited TNF alpha-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 TNFa-induced phosphorylation of Akt (Ser473) and p44/42 MAPK (Thr202/Tyr204). These results suggested that TNFa is expressed in ameloblastoma and it can induce Akt and p44/42 MAPK activation through PIN, which later might induce cell survival and proliferation in ameloblastoma. (c) 2004 Elsevier Ltd. All rights reserved.