Involvement of Oncogenic Protein beta-Catenin in LPS-Induced Cytotoxicity in Mouse Mononuclear Leukemia RAW 264.7 Cells

作者：Koide Naoki^*; Naiki Yoshikazu; Odkhuu Erdenezaya; Tsolmongyn Bilegtsaikhan; Komatsu Takayuki; Ito Kiyoaki; Yoshida Tomoaki; Yokochi Takashi

来源：Oncology Research, 2013, 21(1): 59-65.

DOI：10.3727/096504013X13793555706803

• RAW 264.7 cells
• LPS cytotoxicity
• beta-Catenin
• Endoplasmic reticulum (ER) stress

A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, beta-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3 beta inhibitor, increased LPS-induced beta-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a beta-catenin inhibitor, inhibited LPS-induced beta-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that beta-catenin is involved in LPS-induced cytotoxicity, silencing of beta-catenin expression by siRNA was carried out. The results were that knockdown of beta-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or beta-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2 alpha phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein beta-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.

• 出版日期2013