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One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors.
BACKGROUND
Activator protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2alpha and AP-2gamma is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms.
METHODS
We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant.
RESULTS
We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network.
CONCLUSIONS
Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention.
Ende des Elends in Afrika?
(2010)
Nach 50 Jahren Entwicklungspolitik ist Subsahara-Afrika immer noch im Elend, auch wegen der Entwicklungshilfe. Diese hat oft mehr geschadet als genützt. Mit hunderttausenden Projekten und Milliarden von Hilfsgeldern ist es nicht gelungen, Afrika zu einer selbsttragenden wirtschaftlichen und sozialen Entwicklung zu verhelfen.
Die Dritte Welt in der fossilen Ressourcenfalle – Ressourcenabhängigkeit trotz Ressourcenreichtum
(2010)
Die Städte der Dritten Welt orientierten sich in der nachkolonialen Ära wie selbstverständlich am Vorbild der industriegesellschaftlichen Entwicklung und damit an deren energieintensivem Wachstumsmodell. Dadurch wurden und werden sie unvermittelt und ohne Zeit zur Anpassung einer Wachstumsflut ausgesetzt. Ein beispielloser Zuzug überschwemmt die Städte der Dritten Welt und überfordert in kürzester Zeit ihre Infrastruktur.
Weltentwicklungspolitik – Aufgabe kompetenter und demokratisch legitimierter Globaler Staatlichkeit
(2010)
Global change management: Eine systemische Utopie der Nachhaltigkeit im Angesicht der Apokalypse
(2010)
Für jeden Bürger wird es durch die Berichterstattung in den Medien täglich Realität, dass die globale Welt sich an einem entscheidenden Wendepunkt befindet. Immer mehr Entwicklungsländer werden zu wichtigen Mitspielern auf diesem Globus. Dies hat vielfältige Auswirkungen. So ist auch die traditionelle Entwicklungshilfe einer grundlegenden Prüfung zu unterziehen. Aus der liebgewordenen Nische einer nationalen Politik muss sie sich wandeln zu einem globalen Politikdialog, der mit genau abgestimmten Förderprogrammen verbunden ist. Nur so kann langfristig die Armut wirklich nachhaltig reduziert werden. Der Autor analysiert aber darüber hinaus auch, wie sich in den nächsten Jahrzehnten die wirtschaftlichen und politischen Gewichte zwischen den einzelnen Weltregionen und großen Nationen verschieben werden. Umwelt, Bevölkerungsentwicklung und soziale Lebensbedingungen sind hierbei entscheidende Faktoren. Über eine intensivere regionale Kooperation stellt sich dann aber auch die Frage nach einer stärkeren Rolle der Vereinten Nationen bzw. einer zukünftigen Weltregierung.
Glücksspielrecht im Umbruch
(2010)
Environment monitoring using multiple observation cameras is increasingly popular. Different techniques exist to visualize the incoming video streams, but only few evaluations are available to find the best suitable one for a given task and context. This article compares three techniques for browsing video feeds from cameras that are located around the user in an unstructured manner. The techniques allow mobile users to gain extra information about the surroundings, the objects and the actors in the environment by observing a site from different perspectives. The techniques relate local and remote cameras topologically, via a tunnel, or via bird's eye viewpoint. Their common goal is to enhance spatial awareness of the viewer, without relying on a model or previous knowledge of the environment. We introduce several factors of spatial awareness inherent to multi-camera systems, and present a comparative evaluation of the proposed techniques with respect to spatial understanding and workload.
In this paper, we report on four generations of display-sensor platforms for handheld augmented reality. The paper is organized as a compendium of requirements that guided the design and construction of each generation of the handheld platforms. The first generation, reported in [17]), was a result of various studies on ergonomics and human factors. Thereafter, each following iteration in the design-production process was guided by experiences and evaluations that resulted in new guidelines for future versions. We describe the evolution of hardware for handheld augmented reality, the requirements and guidelines that motivated its construction.
Ab April 2011 erhält die Hochschule Bonn-Rhein-Sieg günstiges Gas von LogoEnergie. Das ist das Ergebnis einer europaweit durchgeführten Ausschreibung, die der Berliner Energie-Broker Ampere AG im Auftrag der öffentlichen Einrichtung durchführte. Durch den Versorgerwechsel erzielt die Hochschule in den kommenden zwei Jahren trotz der schwierigen Marktsituation deutliche Einsparungen bei ihren Energiekosten.