title: Induction of LGR5 by H2O2 treatment is associated with cell proliferation             via the JNK signaling pathway in colon cancer cells.
abstract: Recently, the leucine-rich repeat G protein-coupled receptor 5 (LGR5/GPR49)             was identified as a potential marker of intestinal stem cells in human. The LGR5             is known as a Wnt signaling target gene, and its expression pattern is related             with β-catenin mutation. H2O2 is a member of reactive oxygen species (ROS) and             regulates metabolism, aging, apoptosis and the intensity of growth factor signaling.             In addition, it acts as a negative or positive regulator of Wnt signaling. However,             the effect of H2O2 on Wnt signaling and its target gene LGR5 is not clear. In             this study, we investigated the effects of ROS on cancer stem cells, in colorectal             cancer cells. Colorectal cancer cells were treated with exogenous H2O2, after             which cellular responses and the expression of LGR5 were examined. In SNU-C2A             cells, proliferation increased following treatment with 50-300 µM of H2O2, whereas             cell viability significantly decreased after treatment with 600-900 µM of H2O2.             Expression of heme oxygenase (HO)-1 and jun, which aid in the reduction of oxidative             stress, were induced in the low dose H2O2-treated SNU-C2A cells. The LGR5 expression             level was significantly increased following 50-300 µM H2O2 treatment; in addition,             β-catenin was increased in H2O2-treated colon cancer cells. However, the increased             β-catenin was detected not in the nucleus but in the cytoplasm, which means that             β-catenin was stabilized in the cytoplasm and not translocated into the nucleus             where it could function as a transcription factor for the expression of LGR5.             In addition, there was no direct interaction between LGR5 and β-catenin. In this             study, we found that LGR5 expression increased when cancer cells were treated             with a low dose of H2O2. Our results indicate that the LGR5 increase resulted             via activation of the JNK signaling pathway. The induction of LGR5 expression             influenced cell proliferation in colorectal cancer cells.
authors.affiliation: Laboratory of Cell Biology, Cancer Research Institute, Seoul                     National University College of Medicine, Seoul 110-744, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Byong-Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C116884:LGR5 protein, human; D016877:Oxidants; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin; D006861:Hydrogen Peroxide