Rabbit Anti-Human ERK1/ERK2 (phospho Thr185, Tyr187) monoclonal antibody, clone 26I20M8

Pancreatic cancer (PC) is one of the most malignant cancers worldwide. We describe a novel gene, NOP14, which plays significant roles in PC cell proliferation and migration. Inhibition or overexpression of NOP14 expression in PC cells can reduce or promote motility, proliferation and metastatic capacity in vivo. In parallel, we observed changes in proteins related to migration, such as E-cadherin, vimentin, MMP9, RhoA and p53, along with proteins involved in proliferation, such as MAPK3 and CDK2. Taken together, our study provides new evidence for NOP14 in regulating PC cell proliferation and migration, and may provide new insights for clinical diagnosis and therapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The Ras/Raf/ERK1/2 signaling pathway controls many cellular responses such as cell proliferation, migration, differentiation, and death. In the nervous system, emerging evidence also points to a death-promoting role for ERK1/2 in both in vitro and in vivo models of neuronal death. Recent studies have suggested that abnormal apoptosis in the central nervous system may be involved in the pathogenesis of autism. Two studies reported that both a microdeletion and microduplication on chromosome 16, which includes the MAPK3 gene that encodes ERK1, are associated with autism. In addition, our recent work showed that Ras/Raf/ERK1/2 signaling activities were significantly up-regulated in the frontal cortex of autistic individuals and in the BTBR murine model of autism. To further investigate how Ras/Raf/ERK1/2 up-regulation may lead to the development of autism, we developed a cellular model of Raf/ERK up-regulation by over-expressing c-Raf in cultured cortical neurons (CNs) and cerebellar granule cells (CGCs). We found that Raf/ERK up-regulation stimulates the migration of both CNs and CGCs, and impairs the formation of excitatory synapses in CNs. In addition, we found that Raf/ERK up-regulation inhibits the development of mature dendritic spines in CNs. Investigating the possible mechanisms through which Raf/ERK up-regulation affects excitatory synapse formation and dendritic spine development, we discovered that Raf/ERK up-regulation suppresses the development and maturation of CNs. Together, these results suggest that the up-regulation of the Raf/ERK signaling pathway may contribute to the pathogenesis of autism through both its impairment of cortical neuron development and causing neural circuit imbalances.