Expression changes of BIK in breast cancer tissues of different histological subtypes.

OBJECTIVE: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer. MATERIALS AND METHODS: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues). RESULTS: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells. CONCLUSIONS: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.

OBJETIVO: Determinar el grado de expresión de BIK en tejidos de cáncer de mama de diferente subtipo histológico para ahondar en la participación de BIK en este tipo de cancer. MÉTODO: Por medio de inmunohistoquímica se determinó la expresión de BIK y de su forma fosforilada (p-BIK) en microarreglos de tejidos (tumores [n = 90] y tejidos adyacentes [n = 40]) y líneas celulares. RESULTADOS: Los datos mostraron una sobreexpresión de BIK en los carcinomas de tipo ductal invasivo (grados I, IIA y IIB) y lobular (grados IIA y IIB) con respecto a sus tejidos adyacentes respectivos. En contraste, el carcinoma canalicular (grados I y IIB) y los tumores filoides mostraron una baja expresión de BIK en relación con sus tejidos adyacentes respectivos. El análisis de la qPCR mostró una menor expresión de BIK en las células MCF-10A y MCF-7 en comparación con las células MDA-MB-231 y HMEC. En concordancia con esto, la expresión proteica de BIK fue mayor en las células MDA-MB 231 que en las células MCF-7. CONCLUSIÓN: Nuestros resultados mostraron una asociación entre la expresión de BIK y el subtipo tumoral en estudio, lo cual sugiere una función diferencial de BIK en el cáncer de mama.

Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.

BACKGROUND AND AIMS: Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma. The data was analyzed with the DIANA-miRPath v3.0 platform. RESULTS: The data represented expression changes of all mirRNAs tested in both tumors and blood serum, which strongly suggest their use as circulating biomarkers for astrocytic tumors. The bioinformatic analysis -with DIANA-miRPath v3.0- showed the involvement of these miRNAs in extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer, which control many hallmarks of cancer. In fact, the expression of the proteoglycan syndecan 4 (SDC4) and that of its biosynthetic enzymes, Exostosin Glycosyltransferase 1 (EXT1) and Xylosyltransferase 1 (XYLT1), were altered in pediatric astrocytoma. CONCLUSIONS: Our results highlight the role of microRNAs in the biology of pediatric astrocytoma and demonstrated for the first time the potential use of some circulating microRNAs as non-invasive biomarkers for this type of tumors, particularly miRs 130a, 145, and 335.

Clinical and molecular characterization of a patient with 15q21.2q22.2 deletion syndrome.

We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.

A proteomic approach of pediatric astrocytomas: MiRNAs and network insight.

Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.

El receptor postsináptico de glicina media de forma transitoria y sostenida la inhibición glicinérgica en la retina de los vertebrados / The post-synaptic glycine receptor mediates in a transitory and sustained way the glycinergic inhibition in the vertebrate retina

Introducción. La glicina y el ácido g-aminobutírico son los principales neurotransmisores inhibidores en la retina de los vertebrados. La acción inhibidora de la glicina es mediada por el receptor postsináptico de glicina, que es un canal selectivo al cloruro, constituido por tres subunidades β y dos α (α1 - α4 ) que se antagoniza por el alcaloide estricnina. En la retina se conoce que las cuatro isoformas de la subunidad α se expresan en la capa sináptica interna y que en muy raras ocasiones se localizan en la misma terminal sináptica. Los receptores de glicina formados por las isoformas α1 o α3 poseen cinéticas rápidas, mientras que los receptores α2 o α4 responden tónicamente. El empleo de ratones transgénicos que tienen eliminada (knock-out) o disminuida (knock-down) la expresión de alguno de los genes que codifican para las diferentes isoformas de la subunidad α del receptor de glicina ha permitido estudiar la participación de estas subunidades en la transmisión glicinérgica de la retina de los mamíferos. Objetivo. Describir la participación del receptor de glicina en la neurotransmisión glicinérgica, particularmente en la retina. Desarrollo. En esta revisión se describen los experimentos que han permitido localizar e identificar la participación de los diferentes subtipos del receptor de glicina en circuitos de neurotransmisión específicos en la retina de los vertebrados. Conclusiones. La localización de receptores de glicina constituidos por diferentes isoformas de la subunidad α, en tipos neuronales específicos, indica la presencia de circuitos glicinérgicos que codifican de manera distinta el paso de información en la retina (AU)

Introduction. Glycine and the g-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three β and two α subunits (α1 - α4 ), which is antagonized by the alkaloid strychnine. In the retina, it is known that all α isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either α1 or α3 shows rapid kinetics, whereas α2 or α4 receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor α subunits in the glycinegic neurotransmission of the mammalian retina. Aim. To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. Development. In this review we describe the experiments that have allowed the localization and the involvement of the α subunit isoforms in specific transmission circuits of the vertebrate retina. Conclusions. The localization of the glycine receptor conformed by different isoforms of the α subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina (AU)

[The post-synaptic glycine receptor mediates in a transitory and sustained way the glycinergic inhibition in the vertebrate retina]. / El receptor postsinaptico de glicina media de forma transitoria y sostenida la inhibicion glicinergica en la retina de los vertebrados.

INTRODUCTION: Glycine and the gamma-aminobutyric acid are the principal inhibitory neurotransmitters in the vertebrate retina. The inhibitory action of glycine is mediated by the post-synaptic glycine receptor, a chloride-selective channel, constituted by three beta and two alpha subunits (alpha(1)-alpha(4)), which is antagonized by the alkaloid strychnine. In the retina, it is known that all alpha isoforms are expressed at the level of the inner synaptic layer with a very low colocalization. The glycine receptor formed by either alpha1 or alpha(3) shows rapid kinetics, whereas alpha(2) or alpha(4) receptors respond tonically. The use of transgenic mice has allowed the study of the different glycine receptor alpha subunits in the glycinegic neurotransmission of the mammalian retina. AIM: To describe the participation of the glycine receptor in the inhibitory neurotransmission particularly in the retina. DEVELOPMENT: In this review we describe the experiments that have allowed the localization and the involvement of the alpha subunit isoforms in specific transmission circuits of the vertebrate retina. CONCLUSIONS: The localization of the glycine receptor conformed by different isoforms of the alpha subunit in specific neuronal types, indicate the presence of glycinergic circuits that encode information differently in the retina.

Modulación de los receptores ionotrópicos de tipo cys-loop por proteincinasas A y C / Cys-loop ligand-gated ion channels modulation by protein kinases A and C

Introducción. En el sistema nervioso, la neurotransmisión química rápida es mediada por receptores ionotrópicos que se activan por la unión de su ligando. La unión del ligando a su receptor, favorece la entrada selectiva de iones a la célula que cambia el potencial eléctrico de la membrana celular. Los receptores de tipo cys-loop pertenecen a la superfamilia de receptores ionotrópicos activados por ligando que comprende a los receptores nicotínicos de acetilcolina, del ácido gamma-aminobutírico, glicina, serotonina y zinc. En diversos estudios se demostró que la actividad de estos receptores se modifica en respuesta a la activación de las proteincinasas A y C; los diferentes resultados, aparentemente contradictorios, podrían explicarse por la participación de diversos factores como el tipo de subunidades que forman a los receptores, componentes del citoesqueleto y subtipos de cinasas y fosfatasas presentes en el tejido nervioso de estudio. Objetivo. Presentar una revisión del efecto que las proteincinasas A y C ejercen sobre la actividad de los receptores ionotrópicos de tipo cys-loop. Desarrollo. En esta revisión se describen los experimentos obtenidos en diversas regiones en las que se ha determinado el efecto que tiene la activación de estas cinasas sobre la función de los receptores de neurotransmisores mayormente distribuidos en el sistema nervioso central y que han sido objeto de estudio. Conclusiones. La regulación de los receptores de tipo cys-loop por proteincinasas ocurre por medio de la activación de otros receptores (cross-talk) que se expresan en diversas etapas del desarrollo y áreas del sistema nervioso (AU)

Introduction. In the nervous system, rapid chemical neurotransmission is mediated by ionotropic receptors that are activated by ligand binding. Ligand binding to its receptor promotes the selective flow of ions into the cell which changes the electrical potential of the cell membrane. Cys-loop type receptors belong to the ligand-gated ion channel superfamily including the nicotinic acetylcholine receptor, the gamma-aminobutyric acid, glycine, serotonin and zinc. Several studies showed that the activity of these receptors was modified in response to protein kinases A and C activation; the different results, apparently contradictory, could be explained by the involvement of several factors such as the type of subunits that make up these receptors, components of the cytoskeleton and sub-types of kinases and phosphatases present in nerve tissue studied. Aim. To review the effect of protein kinases A and C on the activity of cys-loop receptors. Development. In this review we describe experiments conducted in different regions where it was determined the effect of these kinases on the function of neurotransmitter receptors mostly distributed in the nervous system. Conclusions. The cys-loop receptors regulation by protein kinases occurs through the activation of other receptors (crosstalk) that are expressed at different stages of development and nervous system areas (AU)