Base de dados : MEDLINE
Pesquisa : D12.644.360.368 [Categoria DeCS]
Referências encontradas : 184 [refinar]
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[PMID]:29227074
[Au] Autor:Minchenko OH; Tsymbal DO; Minchenko DO; Riabovol OO; Ratushna OO; Karbovskyi LL
[Ti] Título:Hypoxic regulation of the expression of cell proliferation related genes in U87 glioma cells upon inhibition of ire1 signaling enzyme
[So] Source:Ukr Biochem J;88(1):11-21, 2016 Ja-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and a controller of cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. It was shown that hypoxia leads to up-regulation of the expression of IL13RA2, CD24, ING1, ING2, ENDOG, and POLG genes and to down-regulation ­ of KRT18, TRAPPC3, TSFM, and MTIF2 genes at the mRNA level in control glioma cells. Changes for ING1 and CD24 genes were more significant. At the same time, inhibition of IRE1 modifies the effect of hypoxia on the expression of all studied genes. In particular, it increases sensitivity to hypoxia of the expression of IL13RA2, TRAPPC3, ENDOG, and PLOG genes and suppresses the effect of hypoxia on the expression of ING1 gene. Additionally, it eliminates hypoxic regulation of KRT18, CD24, ING2, TSFM, and MTIF2 genes expressions and introduces sensitivity to hypoxia of the expression of BET1 gene in glioma cells. The present study demonstrates that hypoxia, which often contributes to tumor growth, affects the expression of almost all studied genes. Additionally, inhibition of IRE1 can both enhance and suppress the hypoxic regulation of these gene expressions in a gene specific manner and thus possibly contributes to slower glioma growth, but several aspects of this regulation must be further clarified.
[Mh] Termos MeSH primário: Estresse do Retículo Endoplasmático/genética
Endorribonucleases/genética
Regulação Neoplásica da Expressão Gênica
Neuroglia/metabolismo
Proteínas Serina-Treonina Quinases/genética
RNA Mensageiro/genética
Transdução de Sinais/genética
[Mh] Termos MeSH secundário: Antígeno CD24/genética
Antígeno CD24/metabolismo
Hipóxia Celular
Linhagem Celular Tumoral
Proliferação Celular
DNA Polimerase gama/genética
DNA Polimerase gama/metabolismo
Endodesoxirribonucleases/genética
Endodesoxirribonucleases/metabolismo
Endorribonucleases/antagonistas & inibidores
Endorribonucleases/metabolismo
Fatores de Iniciação em Eucariotos/genética
Fatores de Iniciação em Eucariotos/metabolismo
Proteínas de Homeodomínio/genética
Proteínas de Homeodomínio/metabolismo
Seres Humanos
Proteína 1 Inibidora do Crescimento/genética
Proteína 1 Inibidora do Crescimento/metabolismo
Subunidade alfa2 de Receptor de Interleucina-13/genética
Subunidade alfa2 de Receptor de Interleucina-13/metabolismo
Queratina-18/genética
Queratina-18/metabolismo
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Neuroglia/patologia
Fatores de Alongamento de Peptídeos/genética
Fatores de Alongamento de Peptídeos/metabolismo
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Qc-SNARE/genética
Proteínas Qc-SNARE/metabolismo
RNA Mensageiro/metabolismo
Receptores Citoplasmáticos e Nucleares/genética
Receptores Citoplasmáticos e Nucleares/metabolismo
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
Proteínas de Transporte Vesicular/genética
Proteínas de Transporte Vesicular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BET1L protein, human); 0 (CD24 Antigen); 0 (Eukaryotic Initiation Factors); 0 (Homeodomain Proteins); 0 (ING1 protein, human); 0 (ING2 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Interleukin-13 Receptor alpha2 Subunit); 0 (KRT18 protein, human); 0 (Keratin-18); 0 (MTIF2 protein, human); 0 (Mitochondrial Proteins); 0 (Peptide Elongation Factors); 0 (Qc-SNARE Proteins); 0 (RNA, Messenger); 0 (Receptors, Cytoplasmic and Nuclear); 0 (TRAPPC3 protein, human); 0 (TSFM protein, human); 0 (Tumor Suppressor Proteins); 0 (Vesicular Transport Proteins); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.7.7 (DNA Polymerase gamma); EC 2.7.7.7 (POLG protein, human); EC 3.1.- (Endodeoxyribonucleases); EC 3.1.- (Endoribonucleases); EC 3.1.21.- (endonuclease G)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.011


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[PMID]:27903908
[Au] Autor:Rajarajacholan UK; Thalappilly S; Riabowol K
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
[Ti] Título:ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization.
[So] Source:Nucleic Acids Res;45(4):1776-1792, 2017 Feb 28.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA transcription by recruiting HDAC1 to rDNA loci, increasing its association with the NoRC complex and deacetylating the histone H3K9 and H3K27 marks of active transcription. Loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GßL, even during rapamycin treatment. ING1 inhibits rDNA transcription by inhibiting UBF activity and its interaction with mTOR. Regulation of rDNA heterochromatin and rRNA synthesis by ING1 is also apparent during normal cell growth and during cell stress. Moreover, this function was also important during PMA induced differentiation of THP1 cells, since knocking down ING1 affected the process by inhibiting rRNA transcriptional repression. These observations show that ING1 regulates the nucleolar epigenome and rDNA transcription suggesting that regulation of protein synthesis might serve as the basis for ING1 function as a type II tumor suppressor.
[Mh] Termos MeSH primário: Cromatina/genética
Cromatina/metabolismo
Regulação da Expressão Gênica
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Nucleares/metabolismo
RNA Ribossômico/genética
Serina-Treonina Quinases TOR/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Diferenciação Celular/genética
Montagem e Desmontagem da Cromatina
Epigênese Genética
Inativação Gênica
Genes Supressores de Tumor
Glucose/metabolismo
Histona Desacetilase 1/metabolismo
Seres Humanos
Proteína 1 Inibidora do Crescimento
Monócitos/citologia
Monócitos/metabolismo
Complexos Multiproteicos/metabolismo
Ligação Proteica
Transporte Proteico
Precursores de RNA/genética
Precursores de RNA/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Multiprotein Complexes); 0 (Nuclear Proteins); 0 (RNA Precursors); 0 (RNA, Ribosomal); 0 (Tumor Suppressor Proteins); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 3.5.1.98 (Histone Deacetylase 1); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw1161


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[PMID]:27305909
[Au] Autor:Esmaeili M; Pungsrinont T; Schaefer A; Baniahmad A
[Ad] Endereço:Institute of Human Genetics, Jena University Hospital, Kollegiengasse 10, 07740, Jena, Germany.
[Ti] Título:A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling.
[So] Source:J Mol Med (Berl);94(10):1167-1179, 2016 Oct.
[Is] ISSN:1432-1440
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The androgen receptor (AR) is a transcriptional factor that has a pivotal role in the development of normal and also cancerous prostate. Therefore, analyzing AR signaling is essential to understand cancerogensis and proliferation of prostate cancer (PCa). Inhibitor of growth 1 (ING1) and ING2 are tumor suppressors with reduced expression in many cancer types. There are also indications of misregulation of ING1 and ING2 in PCa. However, the roles of ING1 and ING2 in PCa and AR signaling are poorly understood. Here, we show that surprisingly the ING1b knockdown (KD) represses AR-mediated transactivation on AR key target genes in the human LNCaP PCa cells. This is associated with growth reduction of LNCaP cells by ING1 KD. In line with this, using Ing1 knockout (KO) mice, we provide further evidence that ING1 deficiency downregulates prostate-specific AR target genes in vivo. Further analyses suggest that KD of ING1b results in induction of both cellular senescence and the cell cycle inhibitor p16 . The unexpected finding that the ING1 KD results in growth inhibition was further analyzed and can be explained by a compensatory mechanism through enhanced levels of ING2 protein in ING1-deficient condition. Accordingly, the data suggest that ING2 interacts with AR and hampers the AR transcriptional activation, causes growth arrest, and induces cellular senescence. The data further suggest that ING2 upregulates p16 , which is a novel target for ING2. Taken together, our data suggest that ING2 is a novel corepressor for AR. ING2 levels are increased upon downregulation of ING1 expression indicating a compensatory mechanism and suggests a novel crosstalk between ING1 and ING2 tumor suppressors to inhibit AR signaling and induce cellular senescence in PCa cells. KEY MESSAGE: • The tumor suppressors ING1 and 2 are dysregulated in human prostate cancer. • ING1 deficiency reduces AR-mediated gene expression in vitro and in vivo. • ING2, like ING1, inhibits AR-mediated transactivation and prostate cancer cell growth. • ING1 regulates ING2. • ING1 and ING2 crosstalk with each other to inhibit AR signaling in prostate cancer.
[Mh] Termos MeSH primário: Proteínas de Homeodomínio/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Nucleares/metabolismo
Receptores Androgênicos/metabolismo
Receptores Citoplasmáticos e Nucleares/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Senescência Celular
Seres Humanos
Proteína 1 Inibidora do Crescimento
Peptídeos e Proteínas de Sinalização Intracelular/genética
Masculino
Camundongos Knockout
Proteínas Nucleares/genética
Próstata/metabolismo
Neoplasias da Próstata/metabolismo
Glândulas Seminais/metabolismo
Transdução de Sinais
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AR protein, human); 0 (AR protein, mouse); 0 (Homeodomain Proteins); 0 (ING1 protein, human); 0 (ING2 protein, human); 0 (ING2 protein, mouse); 0 (Ing1 protein, mouse); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (Receptors, Androgen); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160617
[St] Status:MEDLINE


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[PMID]:26993046
[Au] Autor:Esmaeili M; Jennek S; Ludwig S; Klitzsch A; Kraft F; Melle C; Baniahmad A
[Ad] Endereço:Institute of Human Genetics, Jena University Hospital, Jena, Germany.
[Ti] Título:The tumor suppressor ING1b is a novel corepressor for the androgen receptor and induces cellular senescence in prostate cancer cells.
[So] Source:J Mol Cell Biol;8(3):207-20, 2016 Jun.
[Is] ISSN:1759-4685
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The androgen receptor (AR) signaling is critical for prostate cancer (PCa) progression to the castration-resistant stage with poor clinical outcome. Altered function of AR-interacting factors may contribute to castration-resistant PCa (CRPCa). Inhibitor of growth 1 (ING1) is a tumor suppressor that regulates various cellular processes including cell proliferation. Interestingly, ING1 expression is upregulated in senescent primary human prostate cells; however, its role in AR signaling in PCa was unknown. Using a proteomic approach by surface-enhanced laser desorption ionization-mass spectrometry (SELDI-MS) combined with immunological techniques, we provide here evidence that ING1b interacts in vivo with the AR. The interaction was confirmed by co-immunoprecipitation, in vitro GST-pull-down, and quantitative intracellular colocalization analyses. Functionally, ING1b inhibits AR-responsive promoters and endogenous key AR target genes in the human PCa LNCaP cells. Conversely, ING1b knockout (KO) mouse embryonic fibroblasts (MEFs) exhibit enhanced AR activity, suggesting that the interaction with ING1b represses the AR-mediated transcription. Also, data suggest that ING1b expression is downregulated in CRPCa cells compared with androgen-dependent LNCaP cells. Interestingly, its ectopic expression induces cellular senescence and reduces cell migration in both androgen-dependent and CRPCa cells. Intriguingly, ING1b can also inhibit androgen-induced growth in LNCaP cells in a similar manner as AR antagonists. Moreover, ING1b upregulates different cell cycle inhibitors including p27(KIP1), which is a novel target for ING1b. Taken together, our findings reveal a novel corepressor function of ING1b on various AR functions, thereby inhibiting PCa cell growth.
[Mh] Termos MeSH primário: Senescência Celular
Proteínas Correpressoras/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Nucleares/metabolismo
Neoplasias da Próstata/metabolismo
Neoplasias da Próstata/patologia
Receptores Androgênicos/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Animais
Ciclo Celular/genética
Linhagem Celular Tumoral
Movimento Celular/genética
Proliferação Celular/genética
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Regulação para Baixo/genética
Regulação Neoplásica da Expressão Gênica
Técnicas de Inativação de Genes
Seres Humanos
Proteína 1 Inibidora do Crescimento
Masculino
Camundongos
Células NIH 3T3
Neoplasias da Próstata/genética
Ligação Proteica
Transcrição Genética
Ativação Transcricional/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AR protein, human); 0 (Co-Repressor Proteins); 0 (Cyclin-Dependent Kinase Inhibitor p16); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (Receptors, Androgen); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160320
[St] Status:MEDLINE
[do] DOI:10.1093/jmcb/mjw007


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[PMID]:26720336
[Au] Autor:Boyko A; Riabowol K
[Ad] Endereço:Departments of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
[Ti] Título:A minimal ING1b fragment that improves the efficacy of HDAC-based cancer cell killing.
[So] Source:Cell Death Dis;6:e2027, 2015 Dec 31.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Inibidores de Histona Desacetilases/farmacologia
Peptídeos e Proteínas de Sinalização Intracelular/farmacologia
Proteínas Nucleares/farmacologia
Fragmentos de Peptídeos/farmacologia
Proteínas Supressoras de Tumor/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Sinergismo Farmacológico
Seres Humanos
Proteína 1 Inibidora do Crescimento
Peptídeos e Proteínas de Sinalização Intracelular/química
Proteínas Nucleares/química
Fragmentos de Peptídeos/química
Proteínas Supressoras de Tumor/química
[Pt] Tipo de publicação:NEWS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Histone Deacetylase Inhibitors); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (Peptide Fragments); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160101
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2015.376


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[PMID]:26439691
[Au] Autor:Rajarajacholan UK; Riabowol K
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
[Ti] Título:Aging with ING: a comparative study of different forms of stress induced premature senescence.
[So] Source:Oncotarget;6(33):34118-27, 2015 Oct 27.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cell senescence contributes to organismal aging and is induced by telomere erosion and an ensuing DNA damage signal as cells reach the end of their replicative lifespan in vitro or in vivo. Stresses induced by oncogene or tumor suppressor hyperactivation, oxidative stress, ionizing radiation and other DNA damaging agents result in forms of stress induced premature senescence (SIPS) that show similarities to replicative senescence. Since replicative senescence and SIPS occur over many days and many population doublings of the mass cultures of primary cells used to study senescence, the sequence of events that occur downstream of senescence signaling can be challenging to define. Here we compare a new model of ING1a-induced senescence with several other forms of senescence. The ING1a epigenetic regulator synchronously induces senescence in mass cultures several-fold faster than all other agents, taking 24 and 36 hours to activate the Rb/ p16INK4a, but not the p53 tumor suppressor axis to efficiently induce senescence. ING1a induces expression of intersectin 2, a scaffold protein necessary for endocytosis, altering the stoichiometry of endocytosis proteins, subsequently blocking growth factor uptake leading to activation of Rb signaling to block cell growth. ING1a acts as a novel link in the activation of the Rb pathway that can impose senescence in the absence of activating p53-mediated DNA damage signaling, and should prove useful in defining the molecular events contributing to Rb-induced senescence.
[Mh] Termos MeSH primário: Senilidade Prematura/genética
Senescência Celular/genética
Peptídeos e Proteínas de Sinalização Intracelular/genética
Proteínas Nucleares/genética
Proteína do Retinoblastoma/metabolismo
Estresse Fisiológico/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Proteínas Adaptadoras de Transporte Vesicular/biossíntese
Linhagem Celular
Inibidor p16 de Quinase Dependente de Ciclina/genética
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Dano ao DNA/genética
Endocitose/fisiologia
Células Endoteliais/metabolismo
Seres Humanos
Proteína 1 Inibidora do Crescimento
Queratinócitos/metabolismo
Homeostase do Telômero/genética
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Vesicular Transport); 0 (Cyclin-Dependent Kinase Inhibitor p16); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (ING1 protein, human); 0 (ITSN2 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (Retinoblastoma Protein); 0 (Tumor Suppressor Protein p53); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151007
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.5947


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[PMID]:26306560
[Au] Autor:Thakur S; Nabbi A; Klimowicz A; Riabowol K
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive, Calgary, T2N 4N1, AB, Canada.
[Ti] Título:Stromal ING1 expression induces a secretory phenotype and correlates with breast cancer patient survival.
[So] Source:Mol Cancer;14:164, 2015 Aug 27.
[Is] ISSN:1476-4598
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Previous studies have established that levels of the Inhibitor of Growth 1(ING1) tumor suppressor are reduced in a significant proportion of different cancer types. Here we analyzed levels of ING1 in breast cancer patients to determine its prognostic significance as a biomarker for breast cancer prognosis. METHODS: We used automated quantitative analysis (AQUA) to determine the levels of ING1 in the tumor associated stromal cells of 462 breast cancer samples. To better understand how high ING1 levels affect nearby epithelium, we measured the levels of cytokines and secreted matrix metalloproteases (MMPs), using an ELISA based assay in mammary fibroblasts overexpressing ING1. These cells were also used in a 3-dimensional co-culture with MCF7 cells to determine the effect of released MMPs and other cytokines on growing colonies. RESULTS: We find that high levels of ING1 in stroma are associated with tumor grade (p = 0.001) and size (p = 0.02), and inversely associated with patient survival (p = 0.0001) in luminal, but not in non-luminal cancers, suggesting that high stromal ING1 promotes cancer development. In this group of patients ING1 could also predict patient survival and act as a biomarker (HR = 2.125). While ING1 increased or decreased the expression of different cytokines, ING1 also increased the levels of MMP1, MMP3 and MMP10 by 5-8 fold, and concomitantly decreased levels of the tissue inhibitors of metalloproteases TIMP2, TIMP3 and TIMP4 by 1.5-3.3 fold, resulting in significant increases in MMP activity as determined by zymography. Co-culturing of MCF7 cells with stromal cells expressing ING1 in 3-dimensional organoid cultures suggested that MCF7 colonies were less well defined, suggesting that secreted MMPs might promote migration. CONCLUSION: These data indicate that stromal ING1 expression can predict the survival of patients with luminal breast cancer. High levels of ING1 in stromal cells can promote the development of breast cancer through increased expression and release of MMPs and down regulation of TIMPs, which may be an underlying mechanism of reduced patient survival.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/biossíntese
Neoplasias da Mama/genética
Peptídeos e Proteínas de Sinalização Intracelular/biossíntese
Proteínas Nucleares/biossíntese
Prognóstico
Proteínas Supressoras de Tumor/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/genética
Neoplasias da Mama/patologia
Intervalo Livre de Doença
Feminino
Fibroblastos/metabolismo
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Proteína 1 Inibidora do Crescimento
Peptídeos e Proteínas de Sinalização Intracelular/genética
Células MCF-7
Metaloproteinases da Matriz/biossíntese
Metaloproteinases da Matriz/genética
Meia-Idade
Proteínas Nucleares/genética
Células Estromais/metabolismo
Células Estromais/patologia
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (Tumor Suppressor Proteins); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150827
[St] Status:MEDLINE
[do] DOI:10.1186/s12943-015-0434-x


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[PMID]:25741593
[Au] Autor:Tran UM; Rajarajacholan U; Soh J; Kim TS; Thalappilly S; Sensen CW; Riabowol K
[Ad] Endereço:Department of Biochemistry and Molecular Biology, and Oncology, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1 Alberta, Canada.
[Ti] Título:LincRNA-p21 acts as a mediator of ING1b-induced apoptosis.
[So] Source:Cell Death Dis;6:e1668, 2015 Mar 05.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions.
[Mh] Termos MeSH primário: Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Nucleares/metabolismo
RNA Longo não Codificante/metabolismo
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Apoptose/genética
Apoptose/fisiologia
Linhagem Celular Tumoral
Sobrevivência Celular/genética
Sobrevivência Celular/fisiologia
Imunoprecipitação da Cromatina
Inibidor de Quinase Dependente de Ciclina p21/genética
Seres Humanos
Marcação In Situ das Extremidades Cortadas
Proteína 1 Inibidora do Crescimento
Peptídeos e Proteínas de Sinalização Intracelular/genética
Proteínas Nucleares/genética
Regiões Promotoras Genéticas/genética
Interferência de RNA
RNA Longo não Codificante/genética
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (RNA, Long Noncoding); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150306
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2015.15


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[PMID]:25613480
[Au] Autor:Han X; Chen Y; Yao N; Liu H; Wang Z
[Ad] Endereço:Internal Medicine-Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
[Ti] Título:MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1.
[So] Source:Cancer Gene Ther;22(3):122-9, 2015 Apr.
[Is] ISSN:1476-5500
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of let-7b expression was assessed in vitro in gastric cancer cell lines with let-7b precursor and inhibitor. The roles of let-7b in tumorigenesis and tumor metastasis were analyzed using a stable let-7b expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of let-7b on inhibitor of growth family, member 1 (ING1) expression. Real-time PCR showed decreased levels of let-7b expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7b mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7b could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7b. Luciferase reporter assays demonstrated that let-7b directly binds to the 3'-UTR of ING1, and real-time PCR and western blotting further indicated that let-7b downregulated the expression of ING1 at the mRNA and protein levels. Our study demonstrates that overexpression of let-7b in gastric cancer can inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene ING1. These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that let-7b modulation may be a bona fide treatment of gastric cancer.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Peptídeos e Proteínas de Sinalização Intracelular/genética
MicroRNAs/genética
Proteínas Nucleares/genética
Neoplasias Gástricas/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Adenocarcinoma/metabolismo
Adenocarcinoma/secundário
Animais
Sítios de Ligação
Carcinogênese/genética
Linhagem Celular Tumoral
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Proteína 1 Inibidora do Crescimento
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Nus
Transplante de Neoplasias
Proteínas Nucleares/metabolismo
Interferência de RNA
Neoplasias Gástricas/metabolismo
Neoplasias Gástricas/patologia
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (MicroRNAs); 0 (Nuclear Proteins); 0 (Tumor Suppressor Proteins); 0 (mirnlet7 microRNA, human)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150124
[St] Status:MEDLINE
[do] DOI:10.1038/cgt.2014.75


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[PMID]:25611387
[Au] Autor:Bigot N; Guérillon C; Loisel S; Bertheuil N; Sensebé L; Tarte K; Pedeux R
[Ad] Endereço:1] INSERM U917, Microenvironnement et Cancer, Rennes, France [2] Université de Rennes 1, Rennes, France [3] Etablissement Français du Sang Bretagne, Rennes, France.
[Ti] Título:ING1b negatively regulates HIF1α protein levels in adipose-derived stromal cells by a SUMOylation-dependent mechanism.
[So] Source:Cell Death Dis;6:e1612, 2015 Jan 22.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hypoxic niches help maintain mesenchymal stromal cell properties, and their amplification under hypoxia sustains their immature state. However, how MSCs maintain their genomic integrity in this context remains elusive, since hypoxia may prevent proper DNA repair by downregulating expression of BRCA1 and RAD51. Here, we find that the ING1b tumor suppressor accumulates in adipose-derived stromal cells (ADSCs) upon genotoxic stress, owing to SUMOylation on K193 that is mediated by the E3 small ubiquitin-like modifier (SUMO) ligase protein inhibitor of activated STAT protein γ (PIAS4). We demonstrate that ING1b finely regulates the hypoxic response by triggering HIF1α proteasomal degradation. On the contrary, when mutated on its SUMOylation site, ING1b failed to efficiently decrease HIF1α levels. Consistently, we observed that the adipocyte differentiation, generally described to be downregulated by hypoxia, was highly dependent on ING1b expression, during the early days of this process. Accordingly, contrary to what was observed with HIF1α, the absence of ING1b impeded the adipogenic induction under hypoxic conditions. These data indicate that ING1b contributes to adipogenic induction in adipose-derived stromal cells, and thus hinders the phenotype maintenance of ADSCs.
[Mh] Termos MeSH primário: Tecido Adiposo/citologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Nucleares/metabolismo
Sumoilação
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Hipóxia Celular
Linhagem da Célula
Células Cultivadas
Dano ao DNA
Inativação Gênica
Seres Humanos
Proteína 1 Inibidora do Crescimento
Modelos Biológicos
Proteínas de Ligação a Poli-ADP-Ribose
Proteínas Inibidoras de STAT Ativados/metabolismo
Estabilidade Proteica
Proteólise
Células Estromais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (ING1 protein, human); 0 (Inhibitor of Growth Protein 1); 0 (Intracellular Signaling Peptides and Proteins); 0 (Nuclear Proteins); 0 (PIAS4 protein, human); 0 (Poly-ADP-Ribose Binding Proteins); 0 (Protein Inhibitors of Activated STAT); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150123
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2014.577



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