BACKGROUND/AIM: We have reported that embryonic stem cell-expressed Ras (ERas) is expressed in human gastric cancer and is associated with its tumorigenicity. Here, we asked whether ERas plays a role in resistance to chemotherapy in gastric cancer. MATERIALS AND METHODS: To assess the cytotoxicity of chemotherapeutic agents, ERas-overexpressing human gastric cancer GCIY cells were exposed to anticancer agents, including CPT-11 and inhibitor of mammalian target of rapamycin (mTOR). We also investigated the mechanisms by which ERas induces chemoresistance. RESULTS: ERas-overexpressing clones were significantly more resistant to CPT-11 than were the control (p<0.001). Administration of rapamycin was significantly cytotoxic to the ERas-overexpressing clones compared with the control (p<0.01). Electrophoresis mobility shift assay revealed that ERas enhanced nuclear factor (NF)-κB activity. PCR array demonstrated that ERas up-regulated several multidrug efflux transporter genes, including ABCG2. CONCLUSION: ERas induces chemoresistance to CPT-11 via activation of phosphatidylinositol-3 kinase-protein kinase β mTOR pathway and NF-κB, and consequently results in up-regulation of ABCG2.
BACKGROUND/AIM: We have reported that embryonic stem cell-expressed Ras (ERas) is expressed in humangastric cancer and is associated with its tumorigenicity. Here, we asked whether ERas plays a role in resistance to chemotherapy in gastric cancer. MATERIALS AND METHODS: To assess the cytotoxicity of chemotherapeutic agents, ERas-overexpressing humangastric cancer GCIY cells were exposed to anticancer agents, including CPT-11 and inhibitor of mammalian target of rapamycin (mTOR). We also investigated the mechanisms by which ERas induces chemoresistance. RESULTS:ERas-overexpressing clones were significantly more resistant to CPT-11 than were the control (p<0.001). Administration of rapamycin was significantly cytotoxic to the ERas-overexpressing clones compared with the control (p<0.01). Electrophoresis mobility shift assay revealed that ERas enhanced nuclear factor (NF)-κB activity. PCR array demonstrated that ERas up-regulated several multidrug efflux transporter genes, including ABCG2. CONCLUSION:ERas induces chemoresistance to CPT-11 via activation of phosphatidylinositol-3 kinase-protein kinase β mTOR pathway and NF-κB, and consequently results in up-regulation of ABCG2.
Authors: Daniele Perna; Florian A Karreth; Alistair G Rust; Pedro A Perez-Mancera; Mamunur Rashid; Francesco Iorio; Constantine Alifrangis; Mark J Arends; Marcus W Bosenberg; Gideon Bollag; David A Tuveson; David J Adams Journal: Proc Natl Acad Sci U S A Date: 2015-01-26 Impact factor: 11.205
Authors: Jochen Gaedcke; Andreas Leha; Rainer Claus; Dieter Weichenhan; Klaus Jung; Julia Kitz; Marian Grade; Hendrik A Wolff; Peter Jo; Jérôme Doyen; Jean-Pierre Gérard; Steven A Johnsen; Christoph Plass; Tim Beißbarth; Michael Ghadimi Journal: Oncotarget Date: 2014-09-30
Authors: Gerjon J Ikink; Mandy Boer; Elvira R M Bakker; Annabel Vendel-Zwaagstra; Chris Klijn; Jelle Ten Hoeve; Jos Jonkers; Lodewyk F Wessels; John Hilkens Journal: Oncogene Date: 2018-01-12 Impact factor: 9.867