Suppression of skin tumorigenesis in c-Jun NH2-terminal kinase-2-deficientmice

Previous studies have shown that c-Jun NH2-terminal kinase (JNK) belongs to the mitogen-activated protein kinase (MAPK) family of signal transduction components that are rapidly initiated and activated by many extracellular s timuli. However, the potential role of JNK in mediating tumor promotion and carcinogenesis is unclear. We show here that in JNK2-deficient (Jnk2(-/-)) mice, the multiplicity of papillomas induced by 12-O-tetradecanoylphorbol- 13-acetate (TPA) was lower than that in wildtype mice. Papillomas on wild-t ype mice grew rapidly and were well vascularized compared with Jnk2(-/-) mi ce. After the 12th week of TPA treatment, the mean number of tumors per mou se was 4.13-4.86 in wild-type mice but only 1.13-2.5 in Jnk2(-/-) mice. TPA induced phosphorylation of extracellular signal-regulated kinases and acti vator protein-1 DNA binding activity in wild-type mice, but the phosphoryla tion of extracellular signal-regulated kinases and activator protein-1 DNA binding were inhibited in Jnk2(-/-) mice. These data suggest that JNK2 is c ritical in the tumor promotion process.