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GSE63793
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This serie was performed on liver progenitor isolated based on their expression of the Sca1 surface marker. It contains two independent samples from Rb family deficient liver and three independent samples from control liver, all isolated 2 weeks after Tamoxifen-induced Rb family ablation. Hematopoietic (CD45, Ter119) and endothelial (CD31) markers were used as negative selection markers to exclude blood or endothelial cells from the isolated fraction.
Publication Title
Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Rb family in HSCs results in a severe phenotype, such as enhanced proliferation and increase in stem cell number. In addition, HSCs were higly mobilized but failed to transplant. Rb family deficient mice rapidly exhibit a myeloproliferative disease with eosinophilic characteristics. Meanwhile, the lymphoid compartment was severely decreased, due to high apoptotic activity in this lineage.
Publication Title
Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The retinoblastoma cell cycle regulator pRb and the two related proteins p107 and p130 are thought to suppress cancer development both by inhibiting the G1/S transition of the cell cycle in response to growth-arrest signals and by promoting cellular differentiation. Here, we investigated the phenotype of Rb family triple knock-out (TKO) embryonic stem cells as they differentiate in vivo and in culture. Confirming the central role of the Rb gene family in cell cycle progression, TKO mouse embryos did not survive past mid-gestation and differentiating TKO cells displayed increased proliferation and cell death. However, patterning and cell fate determination were largely unaffected in these TKO embryos. Furthermore, a number of TKO cells, including in the neural lineage, were able to exit the cell cycle in G1 and terminally differentiate. This ability of Rb family TKO cells to undergo cell cycle arrest was associated with the repression of target genes for the E2F6 transcription factor, uncovering a pRb-independent control of the G1/S transition of the cell cycle. These results show that the Rb gene family is required for proper embryonic development but is not absolutely essential to induce G1 arrest and differentiation in certain lineages.
Publication Title
G1 arrest and differentiation can occur independently of Rb family function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Rb family in HSC results in their sustained proliferation, impaired homeostasis and extramedullar mobility.
Publication Title
Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development.
Publication Title
In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Publication Title
The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2).
Publication Title
The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance in early prostate cancer, other factors such as c-Myc and the E2F family also play a role in later stage disease. Hes6 is a transcription co-factor that has been associated with neurogenesis during gastrulation, a neuroendocrine phenotype in the prostate and metastasis in breast cancer but its role in prostate cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and AR and drives castration resistance in prostate cancer. Hes6 activates a cell-cycle enhancing transcriptional network that maintains tumour growth and nuclear AR localization in castrate conditions. We show aphysical interaction between E2F1 and both Hes6 and AR, and suggest a co-dependency of these transcription factors in castration-resistance. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted. We have therefore shown for the first time the critical role of Hes6 in the development of CRPC and identified its potential in patient specific therapeutic strategies.
Publication Title
HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Hes6 is a transcription co-factor that is associated with stem cell characteristics in neural tissue, but its role in cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and the AR and can drive castration resistance in xenografts of the androgen-dependent LNCaP prostate cancer cell line model. Hes6 activates a cell cycle enhancing transcriptional network that maintains tumour growth in the absence of circulating androgen but with maintained nuclear AR. We demonstrate interaction between E2F1, the AR and Hes6 and show the co-dependency of these factors in the castration-resistant setting. In the clinical setting, we have discovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which could be pharmacologically targeted.
Publication Title
HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
We analysed the genexpression of dental follicle cells (DFCs) after 3 days osteogenic differentiation with BMP2 after transfection with a DLX3 plasmid (pDLX3) and after transfection with an empty plasmid (pEV)
Publication Title
A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs).
Sample Metadata Fields
Specimen part
View Samples