Western Blot, chromatin immunoprecipitation

and Luciferase reporter assay were used to examine the regulatory mechanism of β-catenin by Elf3. Results: The elevated mRNA and protein levels of Elf3 were found in CRC tissues, and knockdown of Elf3 induced cell cycle arrest and apoptosis in CRC cell lines. Chromatin immunoprecipitation and Luciferase reporter assay revealed that Elf3 specifically binds to the promoter of β-catenin and activates its transcription. Consistently, knockdown of Elf3 decreased β-catenin expression and significantly suppressed xenograft Selleckchem R428 CRC tumor growth in nude mice. Furthermore, we also found a positive correlation between the expression levels of ELF-3 and β-catenin in human CRC tissue samples. Conclusion: Our data supported the idea that Elf3 functions as an oncogene in colorectal carcinogenesis. Key Word(s): 1. Elf3; 2. beta-catenin; 3. colorectal cancer; 4. oncogene; Presenting Author: DAI YUN Additional find more Authors: ZHANG RONGXIN, QIAO LIANG, TENG GUIGEN, WANG WEIHONG Corresponding Author: DAI

YUN Affiliations: Peking University First Hospital; Tianjing Medical University; University of Sydney at Westmead Hospital Objective: Notch signaling is activated and its primary ligand Jagged1 is highly expressed in various cancers, making Notch pathway a potential therapeutic target. Hence, we aimed to investigate if targeting Jagged1 mediated Notch signaling can offer any therapeutic effect against colorectal cancer (CRC). Methods: Jagged1 expression in human colon cancer tissues was detected by tissue microarray. We constructed a lentiviral vector to deliver small hairpin RNA against Jagged1 (L-Jagged1-shRNA) into colon cancer cells and examined effects of Jagged1 knockdown in vitro and in vivo. Cell

proliferation, migration, and invasion were detected. Cell cycle was determined by flow cytometric analysis. For in vivo studies, nude mice were s.c. inoculated with colon cancer cells with or without Jagged1 knockdown, and tumor growth were measured. Results: Abnormal overexpression of Jagged1 (>2.5 fold) was shown in human CRC tissues compared to non-cancerous colonic tissues. Highly expressed Jagged1 was likely a driving force for increased Notch activity in CRC, as blocking Jagged1 led selleckchem to a marked reduction of Notch target genes. Importantly, L-Jagged1-shRNA rendered a significant reduction of cell proliferation, colony formation, migration and invasion, but only mild apoptosis in colon cancer cells. Knockdown of Jagged1 induced G0/G1 phase cell cycle arrest, with reduced Cyclin D1, Cyclin E and c-Myc expression. The anticancer effect of L-Jagged1-shRNA was further reflected in the in vivo studies, which revealed that down-regulation of Jagged1 inhibited the growth of the xenograft tumors (by >8 fold), and this was associated with a marked downregulation of cell proliferation markers (PCNA, ki-67, and c-Myc) and metastasis markers (MMP-2 and MMP-9).