Herramientas cuantitativas para realizar reconstrucciones ambientales de los rellenos estuarinos recientes usando foraminíferos bentónicos

Con la idea de evaluar la respuesta cuantitativa de los foraminíferos con respecto a la distancia relativa a la boca del estuario (RDEM) en los sistemas estuarinos del sur del Golfo de Vizcaya, se ha desarrollado una función de transferencia basada en un matriz de datos compuesta por 88 muestras y 41 especies obtenidas en seis estuarios del norte de España. La RDEM ha sido considerada como un indicador del gradiente de salinidad. La relación entre los resultados obtenidos e inferidos indica el óptimo funcionamiento de la función de transferencia (r2 jack = 0.76) y permiten llevar a cabo reconstrucciones precisas de la evolución reciente de la RDEM a partir del análisis del registro sedimentari

Sox2 promotes tamoxifen resistance in breast cancer cells

Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo- and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifen-resistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2-expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2-dependent activation of Wnt signalling in cancer stem/progenitor cells

Role of UTX in Retinoic Acid Receptor-Mediated Gene Regulation in Leukemia

Human UTX, a member of the Jumonji C family of proteins, associates with mixed-lineage leukemia 3/4 complexes. Stimulation with retinoic acid leads to the recruitment of UTX-containing complexes to HOX genes, which results in demethylation of histone H3 lysine 27 and concomitant methylation of histone H3 lysine 4. Here, we show that UTX interacts with the retinoic acid receptor α (RARα) and that this interaction is essential for proper differentiation of leukemic U937 cells in response to retinoic acid. UTX occupies the promoters of several RAR target genes and regulates their transcriptional output by modulating ASH2L complex recruitment. Overexpression of UTX in promyelocytic NB4 cells results in enhanced cellular differentiation upon retinoic acid treatment. Our results show that UTX is important for RAR-mediated transcription and provide insight into the critical role of cross talk between histone H3 lysine 4 methylation and histone H3 lysine 27 demethylation during cellular differentiation.Fil: Rocha Viegas, Luciana. Center for Genomic Regulation; España. Universitat Pompeu Fabra; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villa, Raffaella. Center for Genomic Regulation; España. Universitat Pompeu Fabra; EspañaFil: Gutierrez, Arantxa. Center for Genomic Regulation; España. Universitat Pompeu Fabra; EspañaFil: Iriondo, Oihana. Center for Genomic Regulation; España. Universitat Pompeu Fabra; EspañaFil: Shiekhattar, Ramin. University of Miami; Estados UnidosFil: Di Croce, Luciano. Center for Genomic Regulation; España. Universitat Pompeu Fabra; España. Institució Catalana de Recerca i Estudis Avancats; Españ

Effects of estrogen on the proportion of stem cells in the breast

International audienceThere is increasing evidence that breast cancers contain tumor-initiating cells with stem cell properties. The importance of estrogen in the development of the mammary gland and in breast cancer is well known, but the influence of estrogen on the stem cell population has not been assessed. We show that estrogen reduces the proportion of stem cells in the normal human mammary gland and in breast cancer cells. The embryonic stem cell genes , , and are expressed in normal breast stem cells and at higher levels in breast tumor cells and their expression decreases upon differentiation. Overexpression of each stem cell gene reduces estrogen receptor (ER) expression, and increases the number of stem cells and their capacity for invasion, properties associated with tumorigenesis and poor prognosis. These results indicate that estrogen reduces the size of the human breast stem cell pool and may provide an explanation for the better prognosis of ER-positive tumors