@article{67037f999d8249ada410e50eeb02d6da,
title = "Overexpression of Rho effector rhotekin confers increased survival in gastric adenocarcinoma",
abstract = "Like many epithelial-derived cancers, gastric cancer (GC) results from a multistep tumorigenic process. However, the detailed mechanisms involved in GC formation are poorly characterized. Using an ordered differential display method, we have identified rhotekin (RTKN), the gene coding for the Rho effector, RTKN, as one of the genes differentially expressed in human GC. Northern analysis using human multiple tissue blots showed that RTKN is predominantly expressed in the kidney and spinal cord, and, to a lesser degree, in the thyroid, tongue, liver, brain, prostate, trachea, and stomach. RT-PCR analysis confirmed that RTKN was overexpressed in most (5/7; 71%) GC examined. By analyzing the Stanford Microarray Database for the expression profiles of gastric tissues, we also found a progressional increase in RTKN expression in nonneoplastic mucosa, GC, and then lymph node metastases (p <0.005 by Jonckheere-Terpstra test), suggesting that RTKN expression correlates with GC progression. The role of RTKN in the pathogenic development of GC was investigated by transfection and expression of RTKN in AGS gastric cells, which express endogenous RTKN at a low basal level. Flow-cytometric analysis showed that RTKN-transfected AGS cells were significantly more resistant than vector-transfected cells to apoptosis upon treatment with sodium butyrate. To explore the mechanisms underlying RTKN-mediated cell survival, a reporter assay was performed. Since the NF-κB activation is known to promote cell survival and Rho GTPase may lead to NF-κB activation, we transfected AGS cells with the RTKN expression vector along with a pNF-κB-Luc reporter plasmid. Our results showed that overexpression of RTKN induced robust activation of NF-κB, and RTKN-mediated NF-κB activation was suppressed significantly by C3 transferase, an inhibitor of the small GTPase Rho. We conclude that Rho/RTKN-mediated NF-κB activation leading to cell survival may play a key role in gastric tumorigenesis. This study provides original documentation for the overrepresentation of the Rho GTPase effector rhotekin in human cancer and its links to cancer formation. Copyright {\textcopyright} 2004 National Science Council, ROC and S. Karger AG, Basel.",
keywords = "Antiapoptosis, Effectors, Gastric cancer, Nuclear factor-κB, Rho GTPases, butyric acid, immunoglobulin enhancer binding protein, regulator protein, Rho guanine nucleotide binding protein, rhotekin, unclassified drug, apoptosis, article, brain, cancer growth, carcinogenesis, cell survival, controlled study, correlation analysis, data base, differential display, female, flow cytometry, gene expression profiling, gene expression regulation, gene identification, gene overexpression, genetic transfection, human, human cell, human tissue, kidney, liver, lymph node metastasis, male, Northern blotting, plasmid, priority journal, prostate, protein function, reverse transcription polymerase chain reaction, spinal cord, statistical significance, stomach, stomach adenocarcinoma, thyroid gland, tissue distribution, tongue, trachea, Adenocarcinoma, Base Sequence, Cell Survival, DNA Primers, Flow Cytometry, Gene Expression Profiling, Humans, Intracellular Signaling Peptides and Proteins, NF-kappa B, Organ Specificity, Polymerase Chain Reaction, Restriction Mapping, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms, vectors",
author = "Ching-Ann Liu and Mei-Jung Wang and Chin-Wen Chi and Chew-Wun Wu and Jeou-Yuan Chen",
note = "被引用次數：14 Export Date: 28 March 2016 CODEN: JBCIE 通訊地址: Chen, J.-Y.; Institute of Biomedical Sciences, Academia Sinica, 128 Section 2 Yen-Chiu-Yuan Road, Taipei 11529, Taiwan; 電子郵件： bmchen@ibms.sinica.edu.tw 化學物質/CAS: butyric acid, 107-92-6, 156-54-7, 461-55-2; DNA Primers; Intracellular Signaling Peptides and Proteins; NF-kappa B; RTKN protein, human 參考文獻: Bishop, A.L., Hall, A., Rho GTPases and their effector proteins (2000) Biochem J, 348, pp. 241-255; Brizzard, B.L., Chubet, R.G., Vizard, D.L., Immunoaffinity purification of FLAG epitope-tagged bacterial alkaline phosphatase using a novel monoclonal antibody and peptide elution (1994) Biotechniques, 16, pp. 730-735; Cammarano, M.S., Minden, A., Dbl and the Rho GTPases activate NF B by IBB kinase (IKK)-dependent and IKK-independent pathways (2001) J Biol Chem, 276, pp. 25876-25882; Chen, J.-Y., Funk, W.D., Wright, W.E., Shay, J.W., Minna, J.D., Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences (1993) Oncogene, 8, pp. 2159-2166; 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year = "2004",
doi = "10.1159/000079679",
language = "English",
volume = "11",
pages = "661--670",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "5",
}
