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

2005; Elsevier BV; Volume: 332; Issue: 1 Linguagem: Inglês

10.1016/j.bbrc.2005.04.095

1090-2104

Wataru Motomura, Satoshi Tanno, Nobuhiko Takahashi, Miho Nagamine, Mitsuko Fukuda, Yutaka Kohgo, Toshikatsu Okumura,

Metabolism, Diabetes, and Cancer

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.