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GSE29406
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Lactic acidosis and hypoxia are two prominent tumor microenvironmental stresses that are both known to exert important influences on gene expression and phenotypes of cancer cells. But very little is known about the cross-talk and interaction between these two stresses. We performed gene expression analysis of MCF7 cells exposed to lactic acidosis, hypoxia and combined lactic acidosis and hypoxia. We found the hypoxia response elicited under hypoxia was mostly abolished upon simultaneous exposure to lactic acidosis. The repression effects are due to loss of HIF-1 protein synthesis under lactic acidosis. In addition, we showed lactic acidosis strongly synergizes with hypoxia to activate the unfold protein response (UPR) and inflammation response which are highly similar to amino acid deprivation responses (AAR). The statistical factor analysis of hypoxia and lactic acidosis responses indicated that ATF4 locus, an important activator in the UPR/AAR pathway, is amplified in subsets of breast tumors and cancer cell lines. Varying ATF4 levels dramatically affect the ability to survive the post-stress recovery from hypoxia and lactic acidosis and may suggest its selection of ATF4 amplification in human cancers. These data suggest that lactic acidosis interacts with hypoxia by both inhibiting the canonical hypoxia response and while activating the UPR and inflammation response. Gain of ATF4 locus may offer survival advantages to allow successful adaptation to frequent fluctuations of oxygen and acidity in tumor microenvironment. Collectively, our studies have provided linkage between the short-term transcriptional responses to the long term selection of the DNA copy number alterations (CNAs) under tumor microenvironmental stresses.
Publication Title
Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina HiSeq 2500
Description
To explore potential molecular mechanisms underlying the temporal process of DNA damage and repair in CSCs, we utilized deep RNA sequencing to analyze the expression of DNA damage and repair-associated genes at the transcriptome level. Our gene set analysis of CSCs and matched non-CSCs revealed a stemness-associated upward trend of global gene expression, particularly in NHEJ, mismatch excision repair (MMR) and HR pathways. Overall design: The RNA profiles of IN528, T3961, and T4121 CSCs and matched non-CSCs were generated by deep sequencing.
Publication Title
Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
This study examined the gene expression effects of treating androgen-deprived C4-2 prostate cancer cells with the ACLY inhibitor BMS-303141 and the AR antagonist enzalutamide. Overall design: Cells were treated with vehicle control, ACLY inhibitor alone, Enzalutamide alone, and ACLY-inhibitor and Enzalutamide combined together for 24 hours under androgen-depleted conditions (RPMI + 5% charcoal stripped serum). Biological triplicate samples were prepared.
Publication Title
Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.
Sample Metadata Fields
Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection
Publication Title
In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) represent two major approaches for somatic cell reprogramming. However, little attention has been paid to the ability of these two strategies in rejuvenating cells from donors with aging associated syndrome. Here, we utilized telomerase deficient (Terc-/-) mice to probe this question. SCNT-derived embryonic stem cells (ntESCs) and iPSCs were successfully derived from second generation (G2) and third generation (G3) of Terc-/- mice, and ntESCs showed better differentiation potential and self-renewal ability. Telomeres lengthened extensively in cloned embryos while remained or slightly increased in the process of iPSCs induction. Furthermore, G3 ntESCs exhibited improvement of telomere capping function as evidenced by decreased signal free ends and chromosome end-to-end fusion events. In contrast, there was a further decline of telomere capping function in G3 iPSCs. In addition to telomere dysfunction, mitochondria function was severely impaired in G3 iPSCs as evidenced by oxygen consumption rate (OCR) decline, reactive oxygen species (ROS) accumulation and dramatically increased mitochondria genome mutations while these deficiencies were greatly mitigated in G3 ntESCs. Our data proved the principle that SCNT-mediated reprogramming appears more superior than transcription factors induced reprogramming in terms of the resetting of telomere quality and mitochondria function, and thus, providing valuable information for further improvement of transcription factors mediated reprogramming.
Publication Title
Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Differential gene expression profiling in KMT2D-depleted MIA PaCa-2 cells was performed using Human Genome U133 Plus 2.0 Array
Publication Title
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Overall design: Comparison of gene expression at different stages of keratinocyte differentiation
Publication Title
Genome-wide p63-regulated gene expression in differentiating epidermal keratinocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 101 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Carboplatin and paclitaxel are the most widely prescribed chemotherapeutic agents for ovarian cancer. Not all patients respond to treatment, so there is a need for biomarkers that reliably predict resistance in ovarian tumors. Expression of such biomarkers may be dynamically controlled. Gene expression was assessed for a period of 14 days after treatment with carboplatin or combined carboplatin-paclitaxel in xenografts from two ovarian cancer models: chemosensitive serous adenocarcinoma derived OV1002 and slow growing, chemoresistant HOX424 of clear cell origin. Tumour volume reduction was observed in both cell lines post treatment, with a more prominent effect in OV1002, which subsided in late time points. In OV1002, hierarchical clustering classified differentially expressed genes into four time-related patterns, upregulated and downregulated groups for each early and late expressed genes. Upregulated genes were involved in DNA repair, cell cycle and apoptosis, while downregulated groups were involved in oxygen consuming metabolic processes and apoptosis control. Carboplatin-paclitaxel treatment triggered a more comprehensive response. HOX424 responded only to the combined treatment, while the observed reduction in tumour growth was limited. Several apoptosis and cell cycle genes were upregulated, while Wnt signaling was downregulated in the exclusively late expression pattern observed in this cell line. Late downregulated gene groups post carboplatin-taxane treatment were capable of predicting overall survival in two independent clinical datesets. Pathways overrepresented in these clusters were also predictive of outcome. This longitudinal gene expression study may help characterization of chemotherapy response, identification of resistance biomarkers and guiding timing of biopsies.
Publication Title
Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer.
Sample Metadata Fields
Disease, Disease stage, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of the gene expression pattern in the caput, corpus and cauda epididymides of three donors of 26-50 years of age with no medical pathologies that could affect reproductive function. The data generated in this study demonstrate a region specific gene expression pattern along the human epididymis that seems to coincide with the morphological distinctive features of the excurrent duct.
Publication Title
Region-specific gene expression profiling along the human epididymis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The PI3K/mammalian target of rapamycin (mTOR) pathway is dysregulated in over 50% of human GBM but remains a challenging clinical target. Inhibitors against PI3K/mTOR mediators have limited clinical efficacy as single agents. Gene expression profiling after PI3K/mTOR inhibition treatment was analyzed by Affymetrix microarrays.
Publication Title
MSK1-Mediated β-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples