Navegando por Palavras-chave "anoikis"

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    Estudo da expressãode proteínas envolvidas nas vias de sinalização pl3k/akt e ras/erk em células endoteliais resistentes ao anoikis
    (Universidade Federal de São Paulo (UNIFESP), 2014-07-30) Pernambuco Filho, Paulo Castanho de Almeida [UNIFESP]; Azevedo, Carla Cristina Lopes de Azevedo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The acquisition of cell death resistance induced by blocking adhesion to the substrate (anoikis resistance) is a hallmark of neoplastic transformation and a critica I step during the metastatic processo PI3K1AKT and Ras/ERK signaling pathways are directly related to the growth, proliferation and cell survival. Changes in these pathways can also lead to neoplastic transformation. Aiming to clarify the signaling pathways involved in the processes of cell transformation and anoikis, wild endothelial cells (EC) were subjected to transformation induced by blockade of adhesion to the substrate (adhEü) and studied in comparison with endothelial cells transfected with the EJ-ras oncogene (EJ-ras EC) in relation to: cell growth; apoptosis; invasiveness; expression and localization of proteins involved in PI3K/AKT and Ras/ERK pathways. Anoikis resistant cells show characteristics similar to tumorigenic cells: multilayer growth, loss of contact inhibition, tumorigenic capacity, a high invasive potential and a low rate of apoptosis. Treatment with the inhibitor LY294002 led to a decrease in cell growth and increased rates of apoptosis in ali cell types studied. In relation to proteins expression involved in PI3K1AKT and Ras/ERK signaling pathway, Adh-EC clones showed an increase in expression of PI3K, AKT, mTOR, Ras and ERK compared to wild type cells. The expression of these proteins was inhibited after treatment with the inhibitor LY294002 (PI3K, AKT, mTOR) and U0126 (Ras and ERK) in ali cell types. We also observed that the gene expression of PI3K and mTOR is increased and the gene expression of PTEN is decreased in the Adh-EC clones relative to wild type cells. These data suggest that the PI3K1AKT and Ras/ERK signaltng pathways are related to acquisition of resistance to anoikis in endothelial cells. ix
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    Nitric oxide: a potential inducer of adhesion-related apoptosis-anoikis
    (Elsevier B.V., 2004-02-01) Monteiro, H. P. [UNIFESP]; Silva, E. F.; Stern, A.; Universidade Federal de São Paulo (UNIFESP); Univ Paulista; Universidade de São Paulo (USP); NYU
    Among the many initiating events that lead to apoptosis or programmed cell death, loss of contact between the cell and the extracellular matrix has been extensively studied. Adhesion-related apoptosis referred to as anoikis is initiated by the action of anti-adhesive substances. Nitric oxide is one of these anti-adhesive substances that have the capacity to signal and trigger pro-apoptotic events in a variety of cell types. Nitric oxide can inhibit cell adhesion, interfere with the assembly of focal adhesion complexes, and disrupt the cell-extracellular matrix interactions. These actions occur in cell that exhibit a dissociation of growth factor signals from alterations in the cytoskeleton, ultimately leading to apoptosis. Since this involves anti-adhesive events, nitric oxide can be considered as causing anoikis. This review article summarizes the available evidence of how nitric oxide participates in apoptosis induced by loss of anchorage (anoikis). (C) 2004 Elsevier Inc. All rights reserved.
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    Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation
    (Neoplasia Press, 2007-12-01) Campos, Ana Cristina Espindola [UNIFESP]; Molognoni, Fernanda [UNIFESP]; Melo, Fabiana Henrique Machado de [UNIFESP]; Galdieri, Luciano de Camargo [UNIFESP]; Carneiro, Celia Regina Whitaker [UNIFESP]; D'Almeida, Vânia [UNIFESP]; Correa, Mariangela [UNIFESP]; Jasiulionis, Miriam Galvonas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. in this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hcy), an element in the methionine ( universal methyl donor) cycle. This alteration was accompanied by increase in glutathione (GSH) levels and methylated DNA content. Furthermore, a significant increase in dnmt1 and 3b expression was identified along melan-a anchorage blockade. (G)(L)-Nitro-L-arginine methyl esther ((L)-NAME), known as a nitric oxide synthase (NOS) inhibitor, and N-acetyl-(L)-cysteine (NAC) prevented the increase in global DNA methylation, as well as the increase in dnmt1 and 3b expression, observed during melan-a detachment. Interestingly, both (L)-NAME and NAC did not inhibit nitric oxide (NO) production in these cells, but abrogated superoxide anion production during anchorage blockade. in conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism.