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.


METHODS
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 differentiation of PC12 cells and may involve the ERK signaling pathway. This may provide new insights for seeking novel differentiation agents and offer hope for cancer patients.
Yao
Chih-Jung
CJ
Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan, ROC.
Lai
Gi-Ming
GM
Chan
Chin-Feng
CF
Yang
Ya-Yu
YY
Liu
Frank C
FC
Chuang
Shuang-En
SE
D000310:Adrenal Gland Neoplasms / Q000139:chemically induced; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008516:Medicine, Chinese Traditional; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010673:Pheochromocytoma / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014556:Urine
D048049:Extracellular Signal-Regulated MAP Kinases