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GSE42979
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Protein inhibitor of activated STAT3 (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates STAT3 transcriptional activity and cell growth and demonstrates limited expression in the majority of human squamous cell carcinomas of the lung. In the present study we sought to determine if PIAS3 inhibits cell growth in non-small cell lung cancer (NSCLC) cell lines by induction of apoptosis and further determine the dependence of PIAS3 activity on p53 status by using both wild-type and p53-null cells. Our results demonstrate that over-expression of PIAS3 promotes caspase 3 activation and PARP cleavage. Furthermore, the expression of pro-survival family members Bcl-xL and Bcl-2 is decreased. These effects were observed after both transient and regulated expression of exogenous PIAS3 and were independent of p53 status. Furthermore, while p53 can promote apoptosis by inhibition of STAT3 activity, PIAS3 inhibition of STAT3 activity was also p53 independent. Microarray experiments were performed to further investigate the STAT3-dependence of PIAS3-induced apoptosis by comparing the apoptotic gene expression signature induced by PIAS3 over-expression with that induced by STAT3 siRNA. The results showed that a subset of apoptotic genes, including CIDEC and DAPK2, were uniquely expressed only after PIAS3 expression. Thus, PIAS3 may represent a promising lung cancer therapeutic target because of its p53-independent efficacy as well as its potential to synergize with direct STAT3 inhibitors.
Publication Title
PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer cells independent of p53 status.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Targeted therapies have provided advantages to cancer patients, but these therapies are limited by differential responses and developed resistance.
Publication Title
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The primary goal of toxicology and safety testing is to identify agents that have the potential to cause adverse effects in humans. Unfortunately, many of these tests have not changed significantly in the past 30 years and most are inefficient, costly, and rely heavily on the use of animals. The rodent cancer bioassay is one of these safety tests and was originally established as a screen to identify potential carcinogens that would be further analyzed in human epidemiological studies. Today, the rodent cancer bioassay has evolved into the primary means to determine the carcinogenic potential of a chemical and generate quantitative information on dose-response behavior in chemical risk assessments. Due to the resource-intensive nature of these studies, each bioassay costs $2 to $4 million and takes over three years to complete. Over the past 30 years, only 1,468 chemicals have been tested in a rodent cancer bioassay. By comparison, approximately 9,000 chemicals are used by industry in quantities greater than 10,000 lbs and nearly 90,000 chemicals have been inventoried by the U.S. Environmental Protection Agency as part of the Toxic Substances Control Act. Given the disparity between the number of chemicals tested in a rodent cancer bioassay and the number of chemicals used by industry, a more efficient and economical system of identifying chemical carcinogens needs to be developed.
Publication Title
Application of genomic biomarkers to predict increased lung tumor incidence in 2-year rodent cancer bioassays.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
The capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival. Overall design: Haley, J.A., Haughney, E., Ullman, E., Bean, J., Haley, J.D.* and Fink, M.Y. (2014) 'Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant KRas NSCLC Models' Front. Oncology, doi/10.3389/fonc.2014.00344.
Publication Title
Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant-KRas NSCLC Models.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- NextSeq 500
Description
Polycomb repressive complex-2 (PRC2) is a group of proteins that play important role during development and in cell differentiation. PRC2 is a histone-modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co-factor of PRC2 and is important for targeting PRC2 to chromatin as well as modulating its activity. Here, we show that in many human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N-terminal PRC2-interacting domain (?N-JARID2). We show that ?N-JARID2 is a cleaved product of full-length JARID2 spanning the C-terminal conserved region consisting of jumonji domains. JARID2 knockout in keratinocytes results in up-regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID2-null keratinocytes can be relieved by expression of ?N-JARID2 suggesting that this form promotes activation of these genes and has opposing function to that of PRC2 in regulation of differentiation. We propose that a switch from expression of full-length JARID2 to ?N-JARID2 is important for the up-regulation of genes during differentiation. Overall design: RNA-seq analysis of Wildtype and JARID2-null keratinocytes (HaCaTs) on day 0 and day 3 of calcium induced differentiation.
Publication Title
A novel form of JARID2 is required for differentiation in lineage-committed cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
The transcriptomes of FACS-sorted siglec-F+ alveolar macrophages and siglec-f- CD11b+ exudative macrophages from inducible airway GM-CSF over-expressing transgenic mice (DTGM) were compared to non-inducible littermate controls during influenza A virus infection. Overall design: Examination of effect of GM-CSF on airway macrophages during influenza A virus infection
Publication Title
GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
These data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line.
Publication Title
Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We examine the potential of Kras as a metabolic target in lung cancer using the KrasLSL-G12D lung cancer model. We demonstrate that mutant Kras drives a lipogenic gene expression program, and that fatty acid synthesis is important in Kras-induced tumorigenesis.
Publication Title
De novo lipogenesis represents a therapeutic target in mutant Kras non-small cell lung cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression changes were analyzed in 2 acute lymphoblastic leukemia cell lines treated with the GSK126 EZH2 inhibitor using Affymetrix Human Genome U133 Plus 2.0 arrays.
Publication Title
A687V EZH2 is a driver of histone H3 lysine 27 (H3K27) hypertrimethylation.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 82 Downloadable Samples
- Illumina HiSeq 2500
Description
Combined treatment with all-trans retinoic acid and GSK2879552 results in synergistic effects on gene expression, cell proliferation, markers of differentiation, and, most importantly, cytotoxicity. Overall design: Gene expression analysis of DMSO, single and combination treatment (ATRA and GSK2879552) on 6 AML cell lines at two time-points with two replicates (paired end RNA-seq on 96 samples in total)
Publication Title
Lysine specific demethylase 1 inactivation enhances differentiation and promotes cytotoxic response when combined with all-<i>trans</i> retinoic acid in acute myeloid leukemia across subtypes.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples