Correlation of extracellular signal-regulated kinase 2 expression and the cell dissociation induced by dissociation factor in pancreatic cancer cells

Abstract

In our previous studies, the cancer dissociation factor (DF), which can induce cell dissociation of weakly invasive pancreatic cancer cells (PC-1), was isolated from a highly invasive cell line (PC-10). In further study, mitogen-activated protein kinase 2 (MEK2) was discovered to be an invasion-metastasis related factor in this model. Extracellular signal-regulated kinase 2 (ERK2) is known to be the downstream kinase of MEK2 in the mitogen-activated protein kinase (MAPK) signaling pathway. Demonstration of the role of ERK2 in DF induced cell dissociation may contribute to elucidation of the signaling regulatory mechanism of tumor invasion-metastasis. The two cell lines mentioned above and the immunofluorescent method were used. In untreated cells, both total ERK2 and phosphorylated ERK (p-ERK) presented constitutively strong expressions in PC-1.0 cells, whereas the relevant expressions were quite weak in PC-1 cells. Nevertheless, addition of the conditioned medium containing DF to the PC-1 cells, significantly induced total ERK2 and p-ERK expressions and dissociation of islandlike cell colonies. Furthermore, the total ERK2 and p-ERK expressions, either the induced expressions in PC-1 cells or constitutive expressions in PC-1.0 cells, were seriously suppressed after treatment with the MEK2 phosphorylation inhibitor, U0126. Correspondingly, obvious cell colonies formation was observed in these two cell lines. In conclusion, ERK2 activation is closely correlated with the DF induced cell dissociation in pancreatic cancer cells.