Differentiation of Pheochromocytoma PC12 Cells Induced by Human Urine Extract and the Involvement of the Extracellular Signal–Regulated Kinase Signaling Pathway

Objective: The aim of this study was to investigate the effects of a human urine preparation on the differentiation of tumor cells. Design: The pheochromocytoma PC12 cells were used to examine the effects of a human urine preparation, CDA-2 on the induction of differentiation markers, neurofilaments, and compared with that induced by nerve growth factor (NGF). The MAPK/ERK kinase (MEK) inhibitor U0126 was used to examine the involvement of mitogen-activated protein kinase (MAPK) signaling pathway in this differentiation inducing effect. Results: We find that CDA-2 could induce differentiation of pheochromocytoma PC12 cells, as evidenced by the markedly increased expression of neurofilaments to a level comparable to those induced by NGF. This phenomenon was accompanied by the phosphorylation of extracellular-signal–regulated kinase (ERK) and could be inhibited by the MEK inhibitor, U0126. Conclusions: Our results demonstrate the presence of active components in the human urine extract that can induce diffe...