A Potential New Mechanism for Bisphenol Molecules to Initiate Breast Cancer through Alteration of Bone Morphogenetic Protein Signaling in Stem Cells and Their Microenvironment

Endocrine disruptors interfere with endocrine-mediated regulations of cell or organ functions. Estrogens are one of the main hormones altered by endocrine disruptors like bisphenol A (BPA). Stem cells are active from embryogenesis to late stages of adult life. Their unique properties, such as an extended lifespan and low cycling features, render these cell privileged targets of long-term exposure to numerous factors. Therefore, stem cells are likely to be affected following exposure to endocrine disruptors. One of the major signaling pathways involved in stem cell regulation is the bone morphogenetic protein (BMP) pathway. The BMP pathway is known for its involvement in numerous physiological and pathophysiological processes. Exposure of human mammary stem cells to pollutants such as BPA initiates fundamental changes in stem cells, in particular by altering major elements of BMP signaling, such as receptor expression and localization. Lastly, BPA and its substitute bisphenol S (BPS) have similar impacts on BMP signaling despite their different ER-binding properties, supporting the hypothesis that their biological effects cannot be extrapolated only from their interaction with ERα66. We review recent discoveries in this field and discuss their implications for cancer diagnosis, prevention, and treatment, as well as their relevance for studies on endocrine disruptors

Spi-1, Fli-1 and Fli-3 (miR-17-92) Oncogenes Contribute to a Single Oncogenic Network Controlling Cell Proliferation in Friend Erythroleukemia

Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed

In planta gene expression analysis of Xanthomonas oryzae pathovar oryzae, African strain MAI1

<p>Abstract</p> <p>Background</p> <p>Bacterial leaf blight causes significant yield losses in rice crops throughout Asia and Africa. Although both the Asian and African strains of the pathogen, <it>Xanthomonas oryzae </it>pv. <it>oryzae </it>(<it>Xoo</it>), induce similar symptoms, they are nevertheless genetically different, with the African strains being more closely related to the Asian <it>X. oryzae </it>pv. <it>oryzicola </it>(<it>Xoc</it>).</p> <p>Results</p> <p>Changes in gene expression of the African <it>Xoo </it>strain MAI1 in the susceptible rice cultivar Nipponbare were profiled, using an SSH <it>Xoo </it>DNA microarray. Microarray hybridization was performed comparing bacteria recovered from plant tissues at 1, 3, and 6 days after inoculation (dai) with bacteria grown <it>in vitro</it>. A total of 710 bacterial genes were found to be differentially expressed, with 407 up-regulated and 303 down-regulated. Expression profiling indicated that less than 20% of the 710 bacterial transcripts were induced in the first 24 h after inoculation, whereas 63% were differentially expressed at 6 dai. The 710 differentially expressed genes were one-end sequenced. 535 sequences were obtained from which 147 non-redundant sequences were identified. Differentially expressed genes were related to metabolism, secretion and transport, pathogen adherence to plant tissues, plant cell-wall degradation, IS elements, and virulence. In addition, various other genes encoding proteins with unknown function or showing no similarity to other proteins were also induced. The <it>Xoo </it>MAI1 non-redundant set of sequences was compared against several <it>X. oryzae </it>genomes, revealing a specific group of genes that was present only in MAI1. Numerous IS elements were also found to be differentially expressed. Quantitative real-time PCR confirmed 86% of the identified profile on a set of 14 genes selected according to the microarray analysis.</p> <p>Conclusions</p> <p>This is the first report to compare the expression of <it>Xoo </it>genes <it>in planta </it>across different time points during infection. This work shows that as-yet-unidentified and potentially new virulence factors are appearing in an emerging African pathogen. It also confirms that African <it>Xoo </it>strains do differ from their Asian counterparts, even at the transcriptional level.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements