171,555 research outputs found
Abraham C. Reck
No full textAn obituary for publisher and former Iowa state representative Abraham C. Reck
Abraham C. Reck
No full textAn obituary for publisher and former Iowa state representative Abraham C. Reck
Abraham C. Reck
No full textAn obituary for publisher and former Iowa state representative Abraham C. Reck
RECK-Mediated Inhibition of Glioma Migration and Invasion
No full textRECK is an anti-tumoral gene whose activity has been associated with its inhibitory effects regulating MMP-2, MMP-9, and MT1-MMP. RECK level decreases as gliobastoma progresses, varying from less invasive grade II gliomas to very invasive human glioblastoma multiforme (GBM). Since RECK expression and glioma invasiveness show an inverse correlation, the aim of the present study is to investigate whether RECK expression would inhibit glioma invasive behavior. We conducted this study to explore forced RECK expression in the highly invasive T98G human GBM cell line. Expression levels as well as protein levels of RECK, MMP-2, MMP-9, and MT1-MMP were assessed by qPCR and immunoblotting in T98G/RECK+ cells. The invasion and migration capacity of RECK+ cells was inhibited in transwell and wound assays. Dramatic cytoskeleton modifications were observed in the T98G/RECK+ cells, when compared to control cells, such as the abundance of stress fibers (contractile actin-myosin II bundles) and alteration of lamellipodia. T98G/RECK+ cells also displayed phosphorylatecl focal adhesion kinase (P-FAK) in mature focal adhesions associated with stress fibers; whereas P-FAK in control cells was mostly associated with immature focal complexes. Interestingly, the RECK protein was predominantly localized at the leading edge of migrating cells, associated with membrane ruffles. Unexpectedly, introduced expression of RECK effectively inhibited the invasive process through rearrangement of actin filaments, promoting a decrease in migratory ability. This work has associated RECK tumor-suppressing activity with the inhibition of motility and invasion in this GBM model, which are two glioma characteristics responsible for the inefficiency of current available treatments. J. Cell. Biochem. 110: 52-61, 2010. (C) 2010 Wiley-Liss. Inc.FAPESP[06/50915-1]FAPESP[05/51194-3]FAPESP[06/57508-2]CNPqCAPE
RECK regulated endoplasmic reticulum stress response and enhanced cisplatin-induced cell death in neuroblastoma cells
No full textBackground. Reversion:inducing-cysteine-rich protein with Kazal motifs (RECK) is critical for the invasiveness and metastasis of tumor cells; however, its role in regulating the endoplasmic reticulum (ER) stress response remains unclear In this study we investigated the protein that interacts with RECK and the effects of RECK overexpression on the ER stress response and on cisplatin-induced cell death in neuroblastoma cells.
Methods. Full-length RECK (FL-RECK) or a C-terminus-deleted mutant of RECK (del-C-RECK) was transfected into neuroblastoma cells. An immunoprecipitation (IF) assay and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis were used to identify the RECK-interacting proteins. The interaction between RECK and these proteins was confirmed using co-IP and an immunofluorescence assay. Phosphorylation of double-stranded, RNA-activated protein kinase-like, ER-localized eukaryotic initiation factor-2 alpha (eIF-2 alpha) kinase (PERK) and eIF-2 alpha, and expression of ER stress-related apoptotic factors were studied by Western blot analysis.
Results. Glucose-legulated protein 78 (GRP78) was identified as the RECK-interacting protein in neuroblastoma cells, and the C-terminus region of the RECK protein was shown to interact with GRP78. Overexpression of FL-RECK, but not of del-C-RECK, increased the phosphorylation of PERK and eIF-2 alpha in neuroblastoma cells. With cisplatin treatment, the expression of phosphorylated PERK and eIF-2 alpha, CCAAT/enhancer-binding protein-homologous protein, Bax, and caspase-4 and -7 was higher and the cell viability was lower (P < .01) in FL-RECK-overexpressing cells than in del-C-RECK-overexpressing or vector control cells.
Conclusion. RECK regulated the cellular ER stress response through interaction with GRP78 and enhanced cisplatin-induced cell death in neuroblastoma cells
Managing the Development of Computer-Based Systems
No full textIn terms of technical achievement, the computer revolution in U.S. business is outrunning expectations. In terms of economic payoff on new applications, it is rapidly losing momentum. Such is the evidence of a new study by McKinsey & Company of computer systems management in 36 major companies. | From a profit standpoint, their findings indicate computer efforts in all but a few exceptional companies are in real, if often unacknowledged, trouble. Faster, costlier, more sophisticated hardware; larger and increasingly costly computer staffs; and increasingly complex and ingenious applications are in evidence everywhere. | Almost 20 years ago the first computers for business use made their debut. Most large companies have successfully mechanized the bulk of their routine clerical and accounting procedures, and many have moved out into operating applications.ProQuest Traditional Publishing Optio
Molecular mechanism and clinical significance of MYC-induced repression of RECK
No full textThe major cause of therapy failure and death of cancer patients is metastasis. RECK is a newly identified gene which was isolated by screening for human fibroblast cDNA clones giving rise to flat colonies when transfected into v-Ki-ras-transformed NIH3T3 cells. It can inhibit the release and activation of MMP-2 and MMP-9, and prevent cell invasion in vitro. In addition, RECK can repress tumor metastasis in experimental animal. Thus, RECK is a metastasis suppressor gene. However, RECK gene is a common target that is negatively regulated by oncogenic signals. Overexpression of c-myc protooncogene is frequently found in several types of human cancer and contributes to multiple steps of tumorigenesis. Ecto-expression of c-Myc in NIH3T3 cells inhibited RECK expression. Promoter activity assay suggested c-Myc repressed RECK at transcriptional level. By using DNA affinity precipitation assay and chromatin immunoprecipitation assay, we found that oncogenic c-Myc bound to the SP1 sites of RECK promoter in vitro and in vivo. It is possible that c-Myc could repress RECK expression via SP1. Our data suggest that c-Myc may inhibit the metastatic/angiogenic suppressor RECK to enhance cell invasiveness and restoration of RECK may be a novel strategy to inhibit c-Myc-mediated invasion
Mmp17b and Reck are involved in DRG formation.
No full text<p>A, C and E are 26 hpf WISH embryos for <i>mmp17b</i> (A) in red and <i>reck</i> (C) in green. Panel E is a merge of the two images. <i>Reck</i> and <i>mmp17b</i> are expressed near each other in the trunk at this time point. B, D, and F are 26 hpf WISH embryos for <i>mmp17b</i> (B) in red and <i>crestin</i> (D) in green. Panel F is a merge of the two images. <i>Mmp17b</i> and <i>crestin</i> are co-expressed in the trunk at this time point. G, H, and I are confocal image of three color staining of <i>mmp17b</i> (blue), <i>reck</i> (green), and Flk-GFP (red) in the trunk (G) and plexus region (H) of 26 hpf embryos. Asterisks show that <i>mmp17b</i> and <i>reck</i> are expressed next to each other but not in the same cell. Optical section of panel G shown in panel I shows the proximity of <i>mmp17b</i> and <i>reck</i> expression. Panels J-L are cultured HeLa cells on glass coverslips double stained with MMP17 (J, Green) and RECK (K, Red) antibodies. The overlay of image (L) shows both MMP17 and RECK localizes within the cytoplasm in a punctate manner and near the leading edges of the cell indicated by asterisk (*). Image panel stained with DAPI not shown. Scale bar 10 micron.</p
Characterisation of the involvement of the RECK gene on cell proliferation and tumor progression: inverse correlation with the oncogene expression c-myc
No full textEste trabalho mostra o envolvimento do gene RECK no processo de progressão do ciclo celular. Foi verificado que a expressão endógena de RECK é modulada durante a progressão do ciclo celular. A superexpressão de RECK em fibroblastos normais de camundongo promove uma diminuição da capacidade proliferativa das células e um retardo da transição das fases G0/G1-S do ciclo celular. Além disso, os resultados sugerem que um dos possíveis mecanismos de ação de RECK, que promovem este processo, envolve a indução da expressão de um inibidor de CDK, especificamente de p21, e retardo da fosforilação de pRb. Os resultados indicam, ainda, que durante a progressão do ciclo celular a expressão do gene RECK apresenta uma correlação inversa com a expressão do proto-oncogene c-myc. Estes dados corroboram os dados da literatura que mostram RECK como um alvo para o produto de diversos oncogenes, como ras e c-myc. A caracterização da repressão de RECK por c-Myc mostrou que a mesma ocorre ao nível transcricional e que sítios Sp1, presentes no promotor de RECK, são essenciais para a ação de Myc. Dados adicionais sugerem que a repressão de RECK por c-Myc parece envolver mecanismos de desacetilação de histonas. A modulação da expressão de RECK também foi avaliada durante a progressão maligna de tumores do sistema nervoso central (especificamente, gliomas). Foi verificado que a expressão de RECK não é alterada com a progressão deste tipo de tumor. Porém, foi verificado que os pacientes que manifestaram um maior tempo de sobrevida apresentaram tumores com uma significativa maior expressão do gene RECK. Estes dados sugerem que RECK possa ser um possível marcador prognóstico. A caracterização da regulação da expressão de RECK, tanto em células normais como em diferentes tipos de tumores, assim como os alvos moleculares da sua ação, são pontos muito importantes para o entendimento dos mecanismos que controlam a proliferação celular e podem contribuir para o desenvolvimento de novas formas de terapia anti-tumoral.This work shows, for the fIrst time, the involvement of the RECK gene in cell cycle progression. Our data shows that the RECK gene product regulates cell cycle progression by altering the G1 to S transition. Also, we show that RECK is able to induce p21 expression and, consequently, lead to hypophosphorylation of the Rb protein, revealing at least one molecular mechanism through which RECK modulates the cell cycle progression. It has been described that induction of the c-Myc transcription factor promotes cell proliferation and cell transformation by regulating several genes that are involved in cell cycle progression. Here, we show that activation of a Mycestrogen receptor fusion protein with 4-hydroxytamoxifen in mouse fibroblasts was suffIcient to repress the expression of the RECK gene, by acting at the RECK promoter region. In addition, we show that Myc-responsiveness seems to be mediated by the upstream Sp1 sites and to be dependent on cromatin remodelling mechanisms. RECK gene expression was aIso evaluated during human glioma progression. Our results indicate that RECK gene expression is not altered during glioma progresslOn, but a correlation was found between the abundance of RECK expression in gliomas and patient survival. The levels of RECK expression can be considered a good prognostic indicator for glioma patients. Better understanding of RECK gene regulation may contribute to uncover the mechanisms of cell cycle and tumor progression, and to the development of new strategies for cancer prevention and therapeutic intervention
RECK is not an independent prognostic marker for breast cancer
No full textAbstract\ud
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Background\ud
The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear.\ud
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Methods\ud
The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated.\ud
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Results\ud
Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables.\ud
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Conclusions\ud
Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq)Financiadora de Estudos e Projetos (FINEP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Banco Nacional de Desenvolvimento Social e Econômico (BNDES – FUNTEC)Departamento de Ciência e Tecnologia em Saúde - Ministério da Saúde (DECIT-MS) and Ministério da Ciência, Tecnologia e Inovação (MCTI)
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