Epidermal growth factor enhances MPC-83 pancreatic cancer cell migration             through the upregulation of aquaporin 3.
Aquaporin (AQP) water channels are expressed in high-grade tumor cells of             different tissue origins. In this study, we investigated whether AQP3 is expressed             in cultured MPC-83 pancreatic cancer cells, whether AQP3 enhances cell migration             and the signal pathway mechanism involved. MPC-83 pancreatic cancer cells were             pre-treated and treated with EGF at different time points and then analyzed using             western blotting. Results showed that epidermal growth factor (EGF) induced the             phosphorylation of the EGF receptor (EGFR) and extracellular signal-regulated             kinase (ERK), which peaked at 5 min after EGF treatment. EGFR and ERK phosphorylation             induced by EGF were inhibited by PD153035 (EGFR tyrosine kinase inhibitor) and             U0126 (ERK inhibitor), respectively. EGF increased the activity of AQP3 in a dose-             and time-dependent manner in MPC-83 pancreatic cancer cells, which peaked at 24 h             after treatment. The activity of AQP3 and cell migration were inhibited by PD153035,             U0126 and CuSO4 (AQP3 water transport inhibitor). EGFR/ERK pathway-mediated AQP3             activation and cell migration were stimulated by EGF in cultured MPC-83 pancreatic             cancer cells in vitro and this cell signaling pathway is inhibited by the EGFR             and ERK inhibitors, which may be used as potential therapeutic targets in the             treatment of pancreatic cancer.
Department of General Surgery, Kunhua Hospital Affiliated to Kunming Medical College, Kunming, Yunnan 650032, PR China.
Weijun
W
Liu
Kunhua
K
Wang
Kunmei
K
Gong
Xiaogang
X
Li
Kaiyuan
K
Luo
D000970:Antineoplastic Agents / Q000494:pharmacology; D051400:Aquaporin 3 / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D011799:Quinazolines; C113580:U 0126; D051400:Aquaporin 3; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline