Reduction in the cellular levels of the cyclin kinase inhibitor p27kip1 are frequently found in many human cancers and correlate directly with patient prognosis. Specifically ubiquitin dependent proteasomal turnover has been shown to cause reduced p27 expression in many human cancers. We recently demonstated that expression of a stabilized version of p27kip1 (p27kip1T187A) in a genetically modified mouse significantly reduced the number of intestinal adenomatous polyps which progressed to invasive carcinomas. Based on this work we set out to identify compounds which lead to a re-expression of p27 in cancer tissues. In this work we identify Argyrin A a compound derived from myxobacterium archangium gephyra as a potent inducer of p27kip1 expression. Argyrin A induces apoptosis in human colon cancer xenografts and tumor vasculature in vivo leading to a profound reduction in tumor size at well tolerated levels. Argyrin A functions are strictly dependent on the expression of p27kip1 as neither tumor cells nor endothelial cells which do not express p27kip1 respond to this compound. Surprisingly the molecular mechanism by which Argyrin A exerts its p27 dependent biological function is through a potent inhibition of the 20S proteasome.
Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.
Specimen part
View SamplesThe project was designed to identify genes with an altered expression in macrophages from subjects with atherosclerosis compared to macrophages from control subjects.
Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
No sample metadata fields
View SamplesUntreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View SamplesAnalysis of the transcriptome of -catenin flox/- mES cells in comparison with -catenin null mES cells or -catenin null mES cells stably transfected with an E-cadherin--catenin fusion protein.
E-cadherin is required for the proper activation of the Lifr/Gp130 signaling pathway in mouse embryonic stem cells.
Specimen part
View SamplesWe used phytochemical profiling techniques to generate a list of compounds present in each of 13 Equisetum arvense samples sourced globally. We used microarrays to detail the global programme of gene expression underlying the treatment of the model system Saccharomyces cerevisiae to a chosen number of these extracts. A thorough bioinformatic analysis was performed to identify the relationship between phytochemical and gene expression response profiles.
The Saccharomyces cerevisiae transcriptome as a mirror of phytochemical variation in complex extracts of Equisetum arvense from America, China, Europe and India.
No sample metadata fields
View SamplesMM1.S cells stably transduced with control or b-catenin shRNA were established. Total RNA was isolated from 5x 10^6 cells of each in triplicate.
Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
Cell line
View SamplesAnalysis of the transcriptomes of nearly ripe siliques (18-19 DAP) of the rdo2-1, rdo3 and hub1-2 (rdo4) mutants in comparison with wild-type Ler, using Affymetrix GeneChip Arabidopsis ATH1 Genome Array.
Identification of the Arabidopsis REDUCED DORMANCY 2 gene uncovers a role for the polymerase associated factor 1 complex in seed dormancy.
No sample metadata fields
View SamplesAnalysis of the transcriptome of dry hda9-1 mutant seeds with those of Col wild-type seeds, using Affymetrix GeneChip Arabidopsis ATH1 Genome Array.
HISTONE DEACETYLASE 9 represses seedling traits in Arabidopsis thaliana dry seeds.
Specimen part
View SamplesPeriostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity. By differential gene expression we evaluated putative targets involved in those cellular properties.
Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.
Specimen part, Cell line
View SamplesMultiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to impact gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that can prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor a binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine tune the expression of target genes. Overall design: The effects of Enhancer interference (Enhancer-i) and control guide RNA treatment on the transcriptome before and after estrogen treatment, with 2 replicates per condition.
Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.
Specimen part, Treatment, Subject
View Samples