TY - JOUR T1 - Ras-Dependent Recruitment of c-Myc for Transcriptional Activation of Nucleophosmin/B23 in Highly Malignant U1 Bladder Cancer Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1443 LP - 1453 DO - 10.1124/mol.106.024810 VL - 70 IS - 4 AU - Chun-Wei Yeh AU - Sheng-Shun Huang AU - Ru-Ping Lee AU - Benjamin Yat-Ming Yung Y1 - 2006/10/01 UR - http://molpharm.aspetjournals.org/content/70/4/1443.abstract N2 - U1 bladder cancer cells of high malignancy exhibited higher proliferation capacity than U4 premalignant cells. Higher expression of Ras, c-Myc, and nucleophosmin/B23 and greater c-Myc transactivation and nucleophosmin/B23 promoter activities were detected in U1 cells compared with U4 cells. Moreover, c-Myc and nucleophosmin/B23 were increased in U1 but not in U4 cells upon serum stimulation from quiescence. Likewise, only in U1 cells could serum stimulate transcriptional activity of nucleophosmin/B23 promoter and c-Myc response element. The increase of nucleophosmin/B23 promoter activity could be abrogated by mitogen-activated protein kinase/extracellular signal-regulated kinase activating kinase inhibitor and was associated with recruitment of c-Myc to the promoter. U1 cells constitutively expressing dominant-negative Ras reduced the levels of Ras, nucleophosmin/B23, and p-ERK, and consequently abolished the serum-induced up-regulation of nucleophosmin/B23 promoter activity and c-Myc promoter recruitment. Our results indicate that Ras and c-Myc play important roles in the up-regulation of nucleophosmin/B23 during proliferation of cells associated with a high degree of malignancy, thus outlining a signaling cascade involving these factors in the cancer cells. The American Society for Pharmacology and Experimental Therapeutics ER -