Involvement of MEK-ERK signaling pathway in the inhibition of cell growth by troglitazone in human pancreatic cancer cells

Elsevier Inc., Wataru Motomura, Satoshi Tanno, Nobuhiko Takahashi, Miho Nagamine, Mitsuko Fukuda (Sawamukai), Yutaka Kohgo and Toshikatsu Okumura, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 332(1), 2005, 89-94. authorIn the present study, we examined a role of mitogen-activated protein kinases (MAPKs), extracellular signal releted kinase (ERK), c-Jun N-terminal protein kinase (JNK) 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