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GSE55201
Homo sapiens
71 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The effect of anti-IL-17 treatment on systemic inflammation is not fully understand. Using cDNA microarray, genomic analysis methods such as GSEA and ingenuity, we characterized the transcriptional changes in the blood of psoriasis patients afer systemic neutralization of IL-17 compared to baseline (before treatment). We also compared the whole blood-derived transcriptome between psoraisis patients at baseline and healthy volunteers to examine systemic inflammation in psoriasis patients.
Publication Title
IL-17 induces inflammation-associated gene products in blood monocytes, and treatment with ixekizumab reduces their expression in psoriasis patient blood.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGF signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGF activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
Publication Title
HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis, and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGF signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGF activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors.
Publication Title
HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Publication Title
Feedback circuit among INK4 tumor suppressors constrains human glioblastoma development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dual Roles of RNF2 in Melanoma Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms.
Publication Title
Dual Roles of RNF2 in Melanoma Progression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Clinical and genomic evidence support the view that the metastatic potential of a primary tumor may be dictated by transforming events acquired early in the tumorigenic process. It has been proposed that the presence of such pro-metastatic events in early-stage tumors reflects their additional capability to function as oncogenes. Here, to test this deterministic hypothesis and identify potential pro-metastasis oncogenes, we adopted a comparative oncogenomics-guided functional genetic screening strategy involving (i) global transcriptomic data from two genetically engineered mouse models of melanoma with contrasting metastatic potential, (ii) genomic and transcriptomic profiles of human primary and metastatic melanoma and (iii) an invasion screen in TERT-immortalized human melanocytes and melanoma cells in vitro as well as (iv) evidence of expression selection in human melanoma tissues. This integrated effort led to the identification of 6 genes that are both potently pro-invasive and oncogenic. Further, we show that one such pro-invasion oncogene, ACP5, can confer spontaneous metastasis in vivo, engages a key pathway governing metastasis and is prognostic in human primary melanomas.
Publication Title
Proinvasion metastasis drivers in early-stage melanoma are oncogenes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pathologic activation of c-Myc plays a central role in pathogenesis of several neoplasias, including multiple myeloma. However, therapeutic targeting of c-Myc has remained elusive due to its lack of a clear ligand-binding domain. We therefore targeted c-Myc transcriptional function by another means, namely the disruption of chromatin-dependent signal transduction. Members of the bromodomain and extra-terminal (BET) subfamily of human bromodomain proteins (BRD2, BRD3 and BRD4) associate with acetylated chromatin and facilitate transcriptional activation by increasing the effective molarity of recruited transcriptional activators. Notably, BRD4 marks select M/G1 genes in mitotic chromatin for transcriptional memory and direct post-mitotic transcription, via direct interaction with the positive transcription elongation factor complex b (P-TEFb). Because c-Myc is known to regulate promoter-proximal pause release of Pol II, also through the recruitment of P-TEFb, we evaluated the selective small-molecule inhibitor of BET bromodomains, JQ1, as a chemical probe to interrogate the role of BET bromodomains in Myc-dependent transcription and to explore their role as therapeutic targets in c-Myc-driven neoplasias.
Publication Title
BET bromodomain inhibition as a therapeutic strategy to target c-Myc.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target.
Publication Title
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples