@article{oai:nagasaki-u.repo.nii.ac.jp:00016410,
 author = {Kanda, Shigeru and Kanetake, Hiroshi and Miyata, Yasuyoshi},
 issue = {1-2},
 journal = {Molecular and cellular biochemistry},
 month = {Feb},
 note = {Extracellular signal-regulated kinases (ERK) have fundamental roles in tumor progression. However, human clinical trials have shown little or no effect of inhibitors of their upstream signaling molecule, mitogen-activated protein kinase/ERK kinase (MEK), in advanced cancers. To determine the molecular mechanism underlying the limited antitumor effect, we cultured two human renal carcinoma cell lines, ACHN cells and VMRC-RCW cells in the presence of a MEK inhibitor PD98059 for more than 4 weeks (PD98059-exposed cells). PD98059-exposed ACHN cells showed elongated cell shape with scattering morphology, increase in vimentin expression, loss of beta-catenin junctional localization, stress fiber formation, and increased motility. In contrast, VMRC-RCW cells showed scattered phenotype without PD98059-treatment, and this treatment failed to increase the expression of vimentin. Rho A activity was increased in PD98059-exposed ACHN cells. In these cells, enhanced stress fiber formation and motility were observed, both of which were inhibited by treatment with small interfering RNA for Rho A or an Rho kinase inhibitor Y27632. Our results suggest that long-term exposure of human renal carcinoma cells to PD98059 increases cell motility by upregulating Rho A-Rho kinase signaling., Molecular and cellular biochemistry, 309(1-2), pp.69-76; 2008},
 pages = {69--76},
 title = {Long-term exposure of human renal carcinoma cells to PD98059 induces epithelial-mesenchymal transition-like phenotype and enhanced motility.},
 volume = {309},
 year = {2008}
}