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      Role of the ERas gene in gastric cancer cells

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          Abstract

          As a novel member of the Ras family, ERas, found in murine embryonic stem (ES) cells in 2003, was considered a pseudogene. To date, there are a few reports on the relationship between ERas and tumors. It was recently suggested that ERas could affect gastric carcinoma (GC) metastasis, but no significant relationship was found with tumor proliferation. Since ERas plays an important role in tumor-like growth of ES cells subcutaneously injected into nude mice, we hypothesized that ERas plays a role in tumor proliferation. In this experiment, we selected 7 GC strains from different sources with different differentiation degrees, we detected the expression of full length ERas transcript, and selected two ERas highly expressing GC strains, MKN-28 and BGC-823. After knocking down the ERas gene by siRNA, we observed that there was a significant decrease in proliferation, metastasis as well as clonality. Therefore, ERas is confirmed to be an important gene in affecting tumor proliferation and metastasis. Furthermore, the significance of the ERas mechanism and signaling pathway is shown.

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          Most cited references22

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          Phosphatidylinositol-3-OH kinase as a direct target of Ras.

          Ras (p21ras) interacts directly with the catalytic subunit of phosphatidylinositol-3-OH kinase in a GTP-dependent manner through the Ras effector site. In vivo, dominant negative Ras mutant N17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells results in a large elevation in the level of these lipids. Therefore Ras can probably regulate phosphatidylinositol-3-OH kinase, providing a point of divergence in signalling pathways downstream of Ras.
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            Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model.

            Although implantation of fetal dopamine (DA) neurons can reduce parkinsonism in patients, current methods are rudimentary, and a reliable donor cell source is lacking. We show that transplanting low doses of undifferentiated mouse embryonic stem (ES) cells into the rat striatum results in a proliferation of ES cells into fully differentiated DA neurons. ES cell-derived DA neurons caused gradual and sustained behavioral restoration of DA-mediated motor asymmetry. Behavioral recovery paralleled in vivo positron emission tomography and functional magnetic resonance imaging data demonstrating DA-mediated hemodynamic changes in the striatum and associated brain circuitry. These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease.
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              Role of ERas in promoting tumour-like properties in mouse embryonic stem cells.

              Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. Their immortality and rapid growth make them attractive sources for stem cell therapies; however, they produce tumours (teratomas) when transplanted, which could preclude their therapeutic usage. Why ES cells, which lack chromosomal abnormalities, possess tumour-like properties is largely unknown. Here we show that mouse ES cells specifically express a Ras-like gene, which we have named ERas. We show that human HRasp, which is a recognized pseudogene, does not contain reported base substitutions and instead encodes the human orthologue of ERas. This protein contains amino-acid residues identical to those present in active mutants of Ras and causes oncogenic transformation in NIH 3T3 cells. ERas interacts with phosphatidylinositol-3-OH kinase but not with Raf. ERas-null ES cells maintain pluripotency but show significantly reduced growth and tumorigenicity, which are rescued by expression of ERas complementary DNA or by activated phosphatidylinositol-3-OH kinase. We conclude that the transforming oncogene ERas is important in the tumour-like growth properties of ES cells.
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                Author and article information

                Journal
                Oncol Rep
                Oncol. Rep
                Oncology Reports
                D.A. Spandidos
                1021-335X
                1791-2431
                July 2013
                23 April 2013
                23 April 2013
                : 30
                : 1
                : 50-56
                Affiliations
                [1 ]Experimental Research Center, First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China
                [2 ]Shanghai Gezhi High School, Shanghai 200001, P.R. China
                Author notes
                Correspondence to: Dr Huiping Wang or Dr Fang Wei, Experimental Research Center, First People’s Hospital, School of Medicine, Shanghai Jiaotong University, 85 Wujin Road, Shanghai 200080, P.R. China, E-mail: whp9618@ 123456hotmail.com , E-mail: weifang97@ 123456gmail.com
                [*]

                Contributed equally

                Article
                or-30-01-0050
                10.3892/or.2013.2417
                3729207
                23612786
                e445c777-74ed-4dbd-b273-10d780e142a7
                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
                : 28 January 2013
                : 21 March 2013
                Categories
                Articles

                eras,embryonic stem cell,gastric carcinoma,sirna interference

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