Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, a histone deacetylase inhibitor, vorinostat (SAHA), and a hsp90 inhibitor, 17-AAG, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide, vorinostat (SAHA) or 17-AAG, alone or in paired combination, was employed to determine the molecular mechanisms underlying these synergistic interactions.
No associated publication
Cell line
View SamplesZinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis.
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice.
Specimen part
View SamplesAnalysis of root gene expression of salt-tolerant genotypes FL478, Pokkali and IR63731, and salt-sensitive genotype IR29 under control and salinity-stressed conditions during vegetative growth. Results provide insight into the genetic basis of salt tolerance in indica rice.
Root-specific transcript profiling of contrasting rice genotypes in response to salinity stress.
No sample metadata fields
View SamplesThe effect of transient transfection of a construct designed to over-express the androgen receptor (AR) variant AR-V7 on gene expression in MDA-MB-453 cells was assessed using Affymetrix Gene 2.0 ST arrays. Transfection of an AR-expressing construct or an empty construct served as controls.
Expression of androgen receptor splice variants in clinical breast cancers.
Cell line
View SamplesHere we compare the effects of stimulation on cord blood derived CD4+ CD25+ (Treg) and CD4+ CD25- (Thelper) cells, isolated by MACS protocols & expanded in vitro using dynabeads. Expansion was carried out at a ratio of 3 beads/cell in the presence of 1000units/ml of recombinant human IL2 for 8 days, followed by 3 days of culture without beads.
Genome-wide identification of human FOXP3 target genes in natural regulatory T cells.
Specimen part, Treatment
View SamplesThis study has examined the molecular mechanisms underlying sensitivity of sarcomas to Nutlin-3a, a non-genotoxic activator of the p53 pathway. Human patient material was collected immediately following surgical resection, dissected into small pieces and ex planted onto gelatin sponges immersed in media containing either vehicle control or Nutlin-3a (10uM and/or 50uM) for 48 hours.
Nutlin-3a efficacy in sarcoma predicted by transcriptomic and epigenetic profiling.
No sample metadata fields
View SamplesIdentifying the effect of the co-chaperone SGTA on global androgen receptor transcriptional activity in C4-2B prostate cancer cells with view to further elucidating the broader biological role of SGTA on other signaling pathways within prostate cancer cells
Knockdown of the cochaperone SGTA results in the suppression of androgen and PI3K/Akt signaling and inhibition of prostate cancer cell proliferation.
Specimen part, Treatment
View SamplesIn this study we examined the influence of seminal plasma on gene expression in human Ect1 ectocervical epithelial cells, and the extent to which recombinant TGF3 elicits comparable changes. Ect1 cells were incubated with recombinant human TGF3 (5 ng/ml), 10% pooled human seminal plasma (v/v), or medium alone for 10h. RNA was reverse transcribed into cDNA and hybridized to Affymetrix GeneChip Human Genome U133 plus 2.0 microarrays (Affymetrix, Santa Clara, CA). Exposure of Ect1 cells to seminal plasma resulted in differential expression of a total of 3955 probe sets, identified using high stringency criteria with MAS 5.0 analysis. These corresponded to 1338 genes up-regulated and 1343 genes down-regulated by seminal plasma. TGF3 treatment of Ect1 cells resulted in differential expression of 884 probe sets, corresponding to 346 up-regulated genes and 229 down-regulated genes. The genes differentially regulated by seminal plasma included several genes associated with cytokinecytokine receptor interaction, TGF signalling, JAK/STAT signalling or VEGF signalling pathways, as specified by the KEGG database. Of 47 genes in these families, 17 (36.1%) were similarly regulated by both seminal plasma and TGF3. These data, together with additional experiments showing all three TGF isoforms can regulate inflammatory cytokine expression in Ect1 cells, identify TGF isoforms as key agents in seminal plasma that signal induction of pro-inflammatory cytokine synthesis in cervical cells.
TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells.
Cell line, Treatment
View SamplesAbsence of Sox3 in mice only results in subtle phenotype, presumably due to the rescue effects from the family members, SOXB1, which consist of Sox1, Sox2 and Sox3. Obvious defect in Sox3-KO mice is seen only in the testes where Sox1 and Sox2 are not co-expressed. The genetic dysregulation underlying this testis defects is unknown. We also hypothesize that this genetic dysregulation can be rescued by the other SOXB1 members.
No associated publication
Age, Specimen part
View SamplesMutations in the gene encoding the transcription factor AutoImmune REgulator (AIRE) are responsible for the Autoimmune PolyEndocrinopathy Candidiasis Ecodermal Dystrophy syndrome. AIRE directs expression of tissue restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE-deficiency leads to impaired deletion of autospecific T cell precursors. However, a potential role for AIRE in the function of regulatory T cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8+CD28low phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. We here show that CD8+CD28low Treg from AIRE-deficient mice are transcriptionally and phenotypically normal, exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T cell population.
Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.
Treatment
View Samples