MAP2K1 and neuroblastoma: Here we observed that ATRA also induces ERK1/2 phosphorylation in SH-SY5Y human neuroblastoma cells (Figure 2c, right) and we confirmed the key role of ERK1/2 phosphorylation for COX-2 up-regulation by ATRA since treatment with PD098059, the selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK-1), was sufficient to abrogate COX-2 promoter activation, to increase COX-2 protein expression and to increase PGE2 production (Figure 2d and Figure 3a right and 3b).