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

Tumour necrosis factor alpha (TNFα) is known crucial in inducing cell survival, proliferation, differentiation, and apoptosis. In the present study, we found that TNFα as well as its receptors, TNFR1 (TNF Receptor 1) and TNFR2, were clearly expressed in ameloblastoma tissues and AM-1 cells. By stimulation of TNFα in AM-1 cells, the phosphorylation of Akt (Ser473) and p44/42 mitogen-activated protein kinase (MAPK) (Thr202/Tyr204) was markedly increased in TNFα concentration and time dependent manner. Pretreatment with U0126, mitogen-activated extracellular-regulated kinase (MEK) 1/2 inhibitor, prior to TNFα stimulation, specifically inhibited TNFα-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 TNFα-induced phosphorylation of Akt (Ser473) and p44/42 MAPK (Thr202/Tyr204). These results suggested that TNFα 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.