Involvement of MEK-ERK signaling pathway in the inhibition of cell growth by troglitazone in human pancreatic cancer cells.
In the present study, we examined a role of mitogen-activated protein kinases (MAPKs), extracellular signal-related kinase (ERK), c-Jun N-terminal protein kinase, and p38 MAPK in troglitazone-induced inhibition of cell growth in human pancreatic cancer cells. Among the three kinases, troglitazone specifically inhibited the phosphorylation of ERK1/2 in a dose- and time-dependent manner. Troglitazone also down-regulated the protein expression of mitogen-activated protein kinase kinase (MEK)1/2, an upstream molecule that regulates ERK phosphorylation. Treatment of human pancreatic cancer cells with specific MEK inhibitor, PD98059 or U0126, inhibited ERK1/2 phosphorylation and cell growth. These results suggest for the first time that the inhibition of the MEK1/2-ERK1/2 signaling pathway may be implicated in the growth inhibitory effect by troglitazone in human pancreatic cancer cells.
Motomura
Wataru
W
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Tanno
Satoshi
S
Takahashi
Nobuhiko
N
Nagamine
Miho
M
Fukuda
Mitsuko
M
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000008:administration & dosage*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D045162:Thiazolidinediones; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000077288:Troglitazone