Troglitazone increases expression of E-cadherin and claudin 4 in human pancreatic cancer cells.
We examined the effects of troglitazone on expression of E-cadherin and claudin 4 in human pancreatic cancer cells. Troglitazone dose-dependently increased expression of E-cadherin and claudin 4 mRNA and protein in PK-1 cells. Snail, Slug and ZEB1, mRNAs were not changed by troglitazone, indicating that these three transcriptional repressors would not play a role in the induction of E-cadherin by troglitazone. GW9662, a PPARgamma antagonist, failed to block the increased expression of E-cadherin or claudin 4 mRNA, suggesting a PPARgamma-independent pathway. A MEK inhibitor, U0126, increased E-cadherin or claudin 4 mRNA and protein expression, and potently inhibited cell invasion. Because troglitazone down-regulates MEK-ERK signaling and inhibit cell invasion in PK-1 as shown in our previous study, these results suggest that troglitazone increases expression of E-cadherin and claudin 4 possibly through inhibition of MEK-ERK signaling in pancreatic cancer cells, which might be involved in the troglitazone-induced inhibition of cell invasive activity.
Kumei
Shima
S
Department of General Medicine, Asahikawa Medical College, midorigaoka-higashi 2-1-1, Asahikawa, Hokkaido 078-8510, Japan.
Motomura
Wataru
W
Yoshizaki
Takayuki
T
Takakusaki
Kaoru
K
Okumura
Toshikatsu
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D062506:Claudin-4; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002070:Butadienes; C568157:CLDN4 protein, human; D015820:Cadherins; D002839:Chromans; D062506:Claudin-4; D008565:Membrane Proteins; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D045162:Thiazolidinediones; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D000077288:Troglitazone