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      Reduced expression of Rho GDP dissociation inhibitor 2 mRNA is associated with lymph node metastasis in gastric carcinoma

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          Abstract

          Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1 and cdc42, are molecules that have significant roles in linking cell shape and cell cycle progression in cytoskeletal arrangements and mitogenic signaling. Rho GDP dissociation inhibitor 2 (RhoGDI2) has recently been identified as a metastasis suppressor gene in models of bladder cancer. RhoGDI2 has also been identified as a potential regulator of tumorigenesis and cancer progression. The present study aimed to clarify the significance of RhoGDI2 gene expression in gastric carcinoma and to evaluate the outcome of affected patients. A total of 46 pairs of normal mucosa and cancer specimens were obtained from patients who had undergone a gastrectomy for primary gastric carcinoma and were subjected to semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) for RhoGDI2. The expression of RhoGDI2 mRNA was significantly higher in early-stage gastric cancer specimens compared with the normal gastric epithelium samples. By contrast, the depth of the tumor was negatively correlated with RhoGDI2 mRNA expression. In addition, a reduced expression of RhoGDI2 mRNA was associated with venous system invasion and lymph node metastasis. RhoGDI2 mRNA was more frequently expressed in differentiated adenocarcinoma compared with poorly-differentiated adenocarcinoma. Although the statistical significance was not established, RhoGDI2-positive patients tended to have a superior oncological outcome compared with RhoGDI2-negative patients. The reduced expression of RhoGDI2 mRNA in gastric carcinoma is associated with venous system invasion and lymph node metastasis.

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          Japanese Classification of Gastric Carcinoma - 2nd English Edition -

          PREFACE: The first edition of the General Rules for Gastric Cancer Study was published by the Japanese Research Society for Gastric Cancer (JRSGC) in 1963. The first English edition [1] was based on the 12th Japanese edition and was published in 1995. In 1997, the JRSGC was transformed into the Japanese Gastric Cancer Association and this new association has maintained its commitment to the concept of the Japanese Classification. This second English edition was based on the 13th Japanese edition [2].The aim of this classification is to provide a common language for the clinical and pathological description of gastric cancer and thereby contribute to continued research and improvements in treatment and diagnosis.
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            Genomic analysis of metastasis reveals an essential role for RhoC.

            The most damaging change during cancer progression is the switch from a locally growing tumour to a metastatic killer. This switch is believed to involve numerous alterations that allow tumour cells to complete the complex series of events needed for metastasis. Relatively few genes have been implicated in these events. Here we use an in vivo selection scheme to select highly metastatic melanoma cells. By analysing these cells on DNA arrays, we define a pattern of gene expression that correlates with progression to a metastatic phenotype. In particular, we show enhanced expression of several genes involved in extracellular matrix assembly and of a second set of genes that regulate, either directly or indirectly, the actin-based cytoskeleton. One of these, the small GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant-negative Rho or RhoC indicates that RhoC is important in tumour cell invasion. The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis.
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              Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1.

              Professional phagocytes, such as neutrophils and monocytes, have an NADPH oxidase that generates superoxide and other reduced oxygen species important in killing microorganisms. Several components of the oxidase complex have been identified as targets of genetic defects causing chronic granulomatous disease. The complex consists of an electron transport chain that has as its substrate cytosolic NADPH and which discharges superoxide into the cavity of the intracellular phagocytic vacuole. The only electron transport component identified so far is a low-potential cytochrome b, apparently the only membrane component required. At least three cytosolic factors are also necessary, two of which, p67phOx and p47phOx, have been identified by their absence in patients with chronic granulomatous disease. A third component, sigma 1, is required for stimulation of oxidase activity in a cell-free system. The active components of purified sigma 1 are two proteins that associate as heterodimers, and here we report that these are the small GTP-binding protein p21rac1 and the GDP-dissociation inhibitor rhoGDI.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                August 2013
                06 June 2013
                06 June 2013
                : 6
                : 2
                : 463-467
                Affiliations
                Department of Surgery, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
                Author notes
                Correspondence to: Dr Atsuo Shida, Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan, E-mail: atsuoshida@ 123456ybb.ne.jp
                Article
                ol-06-02-0463
                10.3892/ol.2013.1379
                3789053
                24137348
                df8899cc-bc77-4831-bc58-6bb041033f9a
                Copyright © 2013, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 19 December 2012
                : 20 May 2013
                Categories
                Articles

                Oncology & Radiotherapy
                rho gdp dissociation inhibitor 2,gastric carcinoma
                Oncology & Radiotherapy
                rho gdp dissociation inhibitor 2, gastric carcinoma

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