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Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
More effective therapeutic approaches for castration-resistant prostate cancer (CRPC) are urgently needed, thus reinforcing the need to understand how prostate tumors progress to castration resistance. We have established a novel mouse xenograft model of prostate cancer, KUCaP-2, which expresses the wild-type androgen receptor (AR) and which produces the prostate-specific antigen (PSA). In this model, tumors regress soon after castration, but then reproducibly restore their ability to proliferate after 1 to 2 months without AR mutation, mimicking the clinical behavior of CRPC. In the present study, we used this model to identify novel therapeutic targets for CRPC. Evaluating tumor tissues at various stages by gene expression profiling, we discovered that the prostaglandin E receptor EP4 subtype (EP4) was significantly upregulated during progression to castration resistance. Immunohistochemical results of human prostate cancer tissues confirmed that EP4 expression was higher in CRPC compared with hormone-nave prostate cancer. Ectopic overexpression of EP4 in LNCaP cells (LNCaP-EP4 cells) drove proliferation and PSA production in the absence of androgen supplementation in vitro and in vivo. Androgen-independent proliferation of LNCaP-EP4 cells was suppressed when AR expression was attenuated by RNA interference. Treatment of LNCaP-EP4 cells with a specific EP4 antagonist, ONO-AE3-208, decreased intracellular cyclic AMP levels, suppressed PSA production in vitro, and inhibited castration-resistant growth of LNCaP-EP4 or KUCaP-2 tumors in vivo. Our findings reveal that EP4 overexpression, via AR activation, supports an important mechanism for castration-resistant progression of prostate cancer. Furthermore, they prompt further evaluation of EP4 antagonists as a novel therapeutic modality to treat CRPC.
Publication Title
Identification of EP4 as a potential target for the treatment of castration-resistant prostate cancer using a novel xenograft model.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 14 Downloadable Samples
IlluminaHiSeq4000
Description
In zebrafish, parental exposure to ionizing radiation has been associated with effects in offspring, such as increased DNA damage and reactive oxygen species. Here, we assessed short (one month) and long term effects (one year) on gene expression in embryonic offspring (5.5 hours post fertilization) from zebrafish exposed during gametogenesis to gamma radiation (8.7 or 53 mGy/h for 27 days, total dose 5.2 or 31 Gy). One month after exposure, a global change in gene expression was observed in offspring from the 53 mGy/h group, followed by embryonic death at late gastrula, whereas offspring from the 8.7 mGy/h group was unaffected. One year after exposure, embryos from the 8.7 mGy/h group exhibited 2455(61.8% downregulated) differentially expressed genes. Overlaps in differentially expressed genes and enriched biological pathways were evident between the 53 mGy/h group one month and 8.7 mGy/h one year after exposure, which could be linked to effects in adults and offspring, such as DNA damage and lipid peroxidation. Interestingly, pathways between the two groups were oppositely regulated. Our results indicate latent effects following ionizing radiation exposure in parents that can be transmitted to offspring and warrants monitoring effects over subsequent generations. Overall design: One month after exposure, mRNA from F1 5.5 hpf embryos from parents exposed to 8.7 and 53 mGy/h gamma radiation during gametogenesis was sequenced on the Illumina 4000 platform with three replicas per treatment. One year after exposure, mRNA from F1 embryos from the same parents exposed to 8.7 mGy/h was sequenced with three biological replicates. In both cases, F1 embryos from non-exposed parents were used as control and mRNA sequenced in triplicates, taken at the same time points as the exposed samples.
Publication Title
Parental exposure to gamma radiation causes progressively altered transcriptomes linked to adverse effects in zebrafish offspring.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172,780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor.
Publication Title
Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172,780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor.
Publication Title
Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172,780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor.
Publication Title
Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172,780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor.
Publication Title
Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx).
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
We aimed to develop a novel chronic and severe hindlimb ischemia mice model to properly evaluate the therapeutic effects of drug candidates in translational research for critical limb ischemia treatments.
Publication Title
A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates.
Sample Metadata Fields
Specimen part, Time
View Samples
SRP008008- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
small RNA libraries from total RNA isolated from young adult animals Overall design: Wild-type and rem-1 mutant animals were used for RNA isolation. Regular libraries were made using adaptor ligations at both ends. In addition, librraies were made from oxidised and TAP treated RNA.
Publication Title
Differential impact of the HEN1 homolog HENN-1 on 21U and 26G RNAs in the germline of Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples SRP009275- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
small RNA libraries from wild-type and Hen1 mutant testes were made with either polyA tailing (VASAGFPHen1minus/plus) or adapter ligation (Hen1Testis and WTTestis) and sequenced on an Illumina GAII platform. Overall design: RNA was isolated from total testis tissue of both Hen1 wildtype and Hen1 mutant animals. After size selection from gel, the small RNA libraries wre made.
Publication Title
Hen1 is required for oocyte development and piRNA stability in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples