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SRP063573
Homo sapiens
5 Downloadable Samples
IlluminaHiSeq2500
Description
MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf- mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes. Overall design: 5 samples corresponding to mRNA profiles of 501Mel and Hermes3A after BPTF shRNA-mediated knockdown were generated by deep sequencing in triplicate (Hermes 3A) or duplicate (501Mel), using HiSeq2500.
Publication Title
Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 47 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques.
Publication Title
Oxidation reduction is a key process for successful treatment of psoriasis by narrow-band UVB phototherapy.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SRC-1 affects the expression of complex I of the mitochondrial electron transport chain, a set of enzymes responsible for the conversion of NADH to NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer cells abrogated their ability to grow in the absence of glucose consistent with SRC-1's role in promoting cellular adaptation to reduced glucose availability
Publication Title
Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH homeostasis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Disease stage
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In this study, we sought to establish the usefulness of LCM on cDNA microarray analysis. We reported that LCM samples improved the sensitivity of detection of differentially expressed genes over conventional bulk tissue analysis. We also provided the new information of chemokine and its receptor interaction within psoriatic lesional skin.
Publication Title
Combined use of laser capture microdissection and cDNA microarray analysis identifies locally expressed disease-related genes in focal regions of psoriasis vulgaris skin lesions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Purpose: Primary cutaneous squamous cell carcinoma (SCC) can be an invasive cancer in skin and has the potential to metastasize. We aimed to define the cancer related molecular changes that distinguish non-invasive from invasive SCC.
Publication Title
Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the requirement for eIF4E dose at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we surprisingly found that 50% reduction in eIF4E, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation and tumorigenesis. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for eIF4E dose specifically in translating a network of mRNAs enriched for a unique 5UTR signature. In particular, we demonstrate that eIF4E dose is essential for translating mRNAs regulating reactive oxygen species (ROS) that fuel transformation and cancer cell survival in vivo. Therefore, mammalian cells have evolved surplus eIF4E levels that cancer cells hijack to drive a translational program supporting tumorigenesis
Publication Title
Differential Requirements for eIF4E Dose in Normal Development and Cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Each cell type responds uniquely to stress and fractionally contributes to global and tissue-specific stress responses. Hepatocytes, liver macrophages (M), and sinusoidal endothelial cells (SEC) play functionally important and interdependent roles in adaptive processes such as wound healing, obesity, and tumor growth. Although these cell types demonstrate significant phenotypic and functional heterogeneity, their distinctions enabling disease-specific responses remain understudied. To address this, we developed a strategy for simultaneous isolation and quantification of these liver cell types based on antigenic cell surface marker expression in response to DEN and found that while there was only a marginal increase in hepatocyte number, M and SEC populations were quantitatively increased. Global gene expression profiling of hepatocytes, M and SEC identified characteristic gene fingerprints that define each cell type and their distinct physiological or oncogenic stress signatures. Integration of these cell-specific gene fingerprints with available hepatocellular carcinoma (HCC) patient microarray data demonstrates that the hepatocyte-specific response strongly correlates with the human HCC gene expression profile. Liver-specific M and SEC gene signatures demonstrate significant alterations in inflammatory and angiogenic gene regulatory pathways, which may impact the hepatocyte response to oncogenic stress. Further validation confirms alterations in components of two key pathways, AP-1 and p53, that have been previously associated with HCC onset and progression. Our data reveal unique gene expression patterns that serve as molecular fingerprints for the cell-centric responses to pathologic stimuli in the distinct microenvironment of the liver. The technical advance highlighted in this study provides an essential resource for assessing hepatic cell-specific contributions to oncogenic stress, information that could unveil previously unappreciated molecular mechanisms for the cellular crosstalk that underlies the development of hepatic cancer.
Publication Title
Deciphering hepatocellular responses to metabolic and oncogenic stress.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background; Basal cell carcinoma (BCC) is the most common cancer in humans. The pathogenesis of BCC is associated with the sonic hedgehog (SHH) signaling pathway. Vismodegib, a smoothened inhibitor, that targets this pathway is now in clinical use for advanced BCC patients, but its efficacy is limited. Therefore, new therapeutic options for this cancer are required. Methods; We studied gene expression profiling of BCC tumour tissue coupled with laser capture microdissection to identify tumor specific receptor tyrosine kinase expression that can be targeted by small molecule inhibitors. The expression of selected molecules was confirmed by quantitative RT-PCR (qRT-PCR) and by immunohistochemistry. The action of kinase inhibitors was examined on primary normal human epidermal keratinocytes. Results; We found a >250 fold change increase (false discovery rate <10-4) of the oncogene, anaplastic lymphoma kinase (ALK) as well as its ligands, pleiotrophin and midkine in BCC compared to microdissected normal epidermis. qRT-PCR confirmed increased expression of ALK (p<0.05). Stronger staining of phosphorylated ALK in BCC tumour nests than normal skin was observed by immunohistochemistry. Additionally, Crizotinib, an FDA-approved ALK inhibitor, reduced keratinocyte proliferation in culture, whereas a c-Met, another receptor tyrosine kinase, inhibitor did not. Crizotinib significantly reduced the expression of GLI1 and CCND2 mRNA by approximately 60% and 20%, respectively (p<0.05). Conclusions; Our data suggest that ALK may increase GLI1 expression in parallel with the conventional SHH-pathway and promotes keratinocyte proliferation. Furthermore, an ALK inhibitor alone or in combination with targeting SHH-pathway molecules may be a potential treatment for BCC patients.
Publication Title
Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma.
Sample Metadata Fields
Specimen part, Subject
View Samples