Article

TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer

Department of Molecular Carcinogenesis, The Bob Champion Prostate Stem Cell Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
British Journal of Cancer (Impact Factor: 4.82). 12/2008; 99(11):1849-58. DOI: 10.1038/sj.bjc.6604774
Source: PubMed

ABSTRACT Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.

Download full-text

Full-text

Available from: Daniel Brewer, Aug 21, 2015
0 Followers
 · 
148 Views
  • Source
    • "Elevated serum chromogranin A levels are indicative of poor prognosis and decreased survival [20]. Other differentially expressed molecules with prognostic potential include the urokinase plasminogen activation (uPA) [21], TGF-í µí»½1 [22] [23], MUC1 [24], CD24 [25], hCAP-D3 [26], vesicular monoamine transporter 2 (SLC18A2) [27], TEA domain family member 1 (TEAD1), c-Cbl [28], SOX7 and SOX9 [29], nuclear receptor binding protein 1 (NRBP1) [30], CD147 [31], and Wnt5a [32]. Each of these markers will require proper validation to ensure their clinical utility. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS) technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies. We highlight some fundamental issues of translational bioinformatics and the potential use of cloud computing in NGS data processing for the improvement of prostate cancer treatment.
    07/2013; 2013:901578. DOI:10.1155/2013/901578
  • Source
    • "To test for potential association with functional genes, we used the online software blast (Altschul et al. 1990) to investigate similarities between the microsatellite flanking sequences of Lid 8 and Rru 4 and the genome library of zebra fish (Danio rerio, a cyprinid fish biological model). We found that Rru 4 was inserted within a gene sequence coding for transcriptional enhancer factor (TEA) domain family member 1. TEA domain proteins are transcriptional factors that might be implicated in the regulation of cell proliferation (Knight et al. 2008) as well as in the immune response against viral and parasitic infections (Cuddapah, Cui & Zhao 2008). In the case of Lid 8, we found no evidence for a link between a coding gene and Lid 8 microsatellite flanking regions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 1. Understanding the ecological factors driving the burden and pathogenicity of parasites is challenging. Indeed, the dynamics of host–parasite interactions is driven by factors organized across nested hierarchical levels (e.g. hosts, localities), and indirect effects are expected owing to interactions between levels. 2. In this study, we combined Bayesian multilevel models, path analyses and a model selection procedure to account for these complexities and to decipher the relative effects of host- and environment-related factors on the burden and the pathogenicity of an ectoparasite (Tracheliastes polycolpus) on its fish host (Leuciscus leuciscus). We also tested the year-to-year consistency of the relationships linking these factors to the burden and the pathogenic effects of T. polycolpus. 3. We found significant relationships between the parasite burden and host-related factors: body length and age were positively related to parasite burden and heterozygous hosts displayed a higher parasite burden. In contrast, both host- and environment-related factors were linked to pathogenic effects. Pathogenicity was correlated negatively with host body length and positively with age; this illustrates that some factors (e.g. body length) showed inverse relationships with parasite burden and pathogenicity. Pathogenic effects were stronger in cooler upstream sites and where host density was lower. Path analyses revealed that these relationships between environment-related factors and pathogenic effects were direct and were not indirect relationships mediated by the host characteristics. Finally, we found that the strength and the shape of certain relationships were consistent across years, while they were clearly not for some others. 4. Our study illustrates that considering conjointly causal relationships among factors and the hierarchical structure of host–parasite interactions is appropriate for dissecting the complex links between hosts, parasites and their common environment.
    Journal of Animal Ecology 02/2011; 80(3):657-67. DOI:10.1111/j.1365-2656.2011.01804.x · 4.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Global-scale atmospheric circulations illustrate with outstanding clarity one of the grand themes in physics: the organization of chaotic fluctuations in complex dynamical systems, with nontrivial, persistent mean effects. This is a theme recognized as important not just for classical textbook cases like molecular gas kinetics but also for an increasingly wide range of dynamical systems with large phase spaces, not in simple statistical-mechanical equilibrium or near-equilibrium. In the case of the atmosphere, the organization of fluctuations is principally due to three wave-propagation mechanisms or quasi-elasticities: gravity/buoyancy, inertia/Coriolis, and Rossby/vortical. These enter the fluctuation dynamics along with various forms of highly inhomogeneous turbulence, giving rise to a “wave-turbulence jigsaw puzzle” in which the spatial inhomogeneity—characteristic of “wave-breaking” understood in a suitably generalized sense-exhibits phase coherence and is an essential, leading-order feature as illustrated, also, by the visible surf zones near ocean beaches. Such inhomogeneity is outside the scope of classical turbulence theory, which assumes spatial statistical homogeneity or small departures therefrom. The wave mechanisms induce systematic correlations between fluctuating fields, giving rise to mean fluxes or transports of momentum quite different from those found in gas kinetics or in classical turbulence theory. Wave-induced momentum transport is a long-range process, effective over distances far exceeding the fluctuating material displacements or “mixing lengths” characteristic of the fluid motion itself. Such momentum transport, moreover, often has an “anti-frictional” character, driving the system away from solid rotation, not toward it, as underlined most plainly by the existence of the stratospheric quasi-biennial oscillation (QBO) and its laboratory couunterparts.Wave-induced momentum transport drives the Coriolis-mediated “gyroscopic pumping” of meridional circulations against radiative relaxation, as illustrated by the Murgatroyd-Singleton mesospheric circulation and the Brewer-Dobson (misnamed Hadley) stratospheric circulation. The Brewer-Dobson can be contrasted with the convectively driven tropospheric Hadley circulation and with the oceans' thermohaline circulation. The ocean is an opposite extreme case in the sense that radiative relaxation has no counterpart. If the stratosphere is compared to a tape recorder whose motor is the gyroscopic pump and whose recording head is the tropical tropopause with its seasonal water-vapour signal, then the distribution of radiative-equilibrium temperatures across the tropics may be compared to the guidance wheels influencing the upward path of the tape. In other words, solar heating does not drive the tropical stratospheric upwelling, but does influence the way in which the upwelling mass flux demanded by the wave-driven pumping is distributed across the tropics. Because the tropical mean circulation problem is nonlinear, one cannot think of the tropical part of the circulation as a linear superposition of thermally and mechanically driven “contributions”.Insights into the dynamics of atmospheric circulations have recently led to a breakthrough in an astrophysical problem, that of understanding the differential rotation, meridional circulation, and helium distribution within the sun, with strong implications for helioseismic inversion and the so-called lithium and beryllium problems. This is an example of meteorological understanding informing solar and stellar physics.
Show more