Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA.
Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer.
Specimen part, Cell line
View SamplesTargets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Treatment
View SamplesWe used microarrays to examine gene expression levels from 95 unrelated CEPH-Utah individuals 0, 2 or 6 hours after treatment with 10Gy of ionizing radiation.
Stress-induced changes in gene interactions in human cells.
Cell line, Treatment, Time
View SamplesWe used microarrays to examine gene expression levels from 131 unrelated CEPH-Utah grandparents with either DMSO or tunicamycin.
Stress-induced changes in gene interactions in human cells.
Cell line, Treatment, Time
View SamplesThyroid hormones, thyroxine and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1,145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way we could identify genomic targets of T3 in astrocytes and neurons, and in neuron subtypes, such as layer-specific neurons, and neurons expressing specific markers such as prepronociceptin, cholecystokinin, or cortistatin. T3 up-regulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport, and down-regulates genes involved in nuclear events, such as cell division, M phase of cell cycle, and chromosome organization and segregation. Remarkably the transcriptomic changes induced by T3 sustain the transition from embryonic to adult patterns of gene expression. The results allowed us to define in molecular terms the elusive role of thyroid hormones on neocortical development. Overall design: Pregnant dams were euthanized on gestational day 17.5, and the fetuses were extracted and euthanized by decapitation. The cerebral cortices were dissected, disaggregated and finally the cells were suspended in culture medium. After 9 days incubation cells were incubated for 24 hours before adding T3 at a final concentration of 10 nM. The cells were harvested 24 hours later. Cells without T3 were incubated in parallel. Cerebral cortices from individual fetuses originated two replicas for the cell culture, one with T3 and another without T3. Number of samples: 6.
Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.
No sample metadata fields
View SamplesHow cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of WNT signaling upon knock-down (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFa as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the membrane localization, and thus function, of TGFa. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFa exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFa ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFa and GLI1 that enhances metastases. We suggest that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities. Overall design: CC14 and CC36, two primary colon cancer cells, were treated with control or shTMED9 expressing lentivirus. In addition, CC14 cells were also treated with shTMED3 expressing lentivirus. All the experiments were run in triplicates totaling 15 Samples.
The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.
Specimen part, Disease stage, Subject
View SamplesOur findings demonstrate that CDCP1 is a novel modulator of HER2 signalling, and a biomarker for the stratification of breast cancer patients with poor prognosis
Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.
Cell line
View SamplesHemophagocytes are activated macrophages seen morphologically to have engulfed other hematopoietic cells. Their function is unknown. Attempts to induce these cells in vitro or purify them ex vivo have been unsuccessful.
Brief report: alternative activation of laser-captured murine hemophagocytes.
Sex, Age, Specimen part
View Samplesassess the efficacy of Pimasertib to characterize its mechanism of action
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Cell line, Treatment, Time
View SamplesWe individually examined the ability of human ARGFX, DPRX, LEUTX, and TPRX1 to regulate gene expression by ectopically expressing these proteins in fibroblasts. Overall design: Each gene along with an empty control vector were transfected individually to drive ectopic expression in human dermal fibroblasts, in triplicate.
Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals.
Specimen part, Subject
View Samples