PMID- 21965746
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20181201
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 31
IP  - 10
DP  - 2011 Oct
TI  - ERas enhances resistance to CPT-11 in gastric cancer.
PG  - 3353-60
AB  - 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)-kappaB 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 beta mTOR pathway and NF-kappaB, and 
      consequently results in up-regulation of ABCG2.
FAU - Kubota, Eiji
AU  - Kubota E
AD  - Department of Gastroenterology and Metabolism, Nagoya City University, Graduate 
      School of Medical Sciences. 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan.
FAU - Kataoka, Hiromi
AU  - Kataoka H
FAU - Tanaka, Mamoru
AU  - Tanaka M
FAU - Okamoto, Yasuyuki
AU  - Okamoto Y
FAU - Ebi, Masahide
AU  - Ebi M
FAU - Hirata, Yoshikazu
AU  - Hirata Y
FAU - Murakami, Kenji
AU  - Murakami K
FAU - Mizoshita, Tsutomu
AU  - Mizoshita T
FAU - Shimura, Takaya
AU  - Shimura T
FAU - Mori, Yoshinori
AU  - Mori Y
FAU - Tanida, Satoshi
AU  - Tanida S
FAU - Kamiya, Takeshi
AU  - Kamiya T
FAU - Aoyama, Mineyoshi
AU  - Aoyama M
FAU - Asai, Kiyofumi
AU  - Asai K
FAU - Joh, Takashi
AU  - Joh T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - 7673326042 (Irinotecan)
RN  - 9007-49-2 (DNA)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - EC 5.99.1.2 (DNA Topoisomerases, Type I)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Camptothecin/*analogs & derivatives/pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - DNA/metabolism
MH  - DNA Topoisomerases, Type I/metabolism
MH  - Drug Resistance, Neoplasm/drug effects/genetics
MH  - Embryonic Stem Cells/drug effects/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Irinotecan
MH  - Models, Biological
MH  - NF-kappa B/metabolism
MH  - Protein Binding/drug effects
MH  - Sirolimus/pharmacology
MH  - Stomach Neoplasms/*drug therapy/genetics/pathology
MH  - Up-Regulation/drug effects
MH  - ras Proteins/*metabolism
EDAT- 2011/10/04 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/10/04 06:00
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 31/10/3353 [pii]
PST - ppublish
SO  - Anticancer Res. 2011 Oct;31(10):3353-60.