8 NSCLC cell lines treated with either 50nM or 100nM of AUY for 24 hours.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Habib Hamidi
PROVIDER: E-GEOD-43568 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:34 NSCLC cell lines were transcriptionally profiled against a reference mix of 45 NSCLC cell lines to look subtype specific differential gene expression 34 individual cell lines were compared to a reference mix consiting of 45 NSCLC cell lines
2013-01-18 | E-GEOD-43567 | biostudies-arrayexpress
Project description:PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer. We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovarian cancer cell lines. Molecular markers for response prediction, including p16 and Rb, were studied using gene expression profiling, Western blot, and arrayCGH. Multiple drug effect analysis was used to study interactions with chemotherapeutic drugs. Expression of p16 and Rb was studied using immunohistochemistry in a large clinical cohort ovarian cancer patients. Concentration-dependent anti-proliferative effects of PD-0332991were seen in all ovarian cancer cell lines, but varied significantly between individual lines. Rb proficient cell lines with low p16 expression were most responsive to CDK4/6 inhibition. Copy number variations of CDKN2A, Rb, CCNE1, and CCND1 were associated with response to PD-0332991. CDK4/6 inhibition induced G0/G1 cell cycle arrest, blocked Rb phosphorylation in a concentration and time dependent manner, and enhanced the effects of chemotherapy. Rb proficiency with low p16 expression was seen in 97/262 (37%) of ovarian cancer patients and associated with adverse clinical outcome (progression free survival, adjusted relative risk 1.49, 95%CI 0.99-2.22, p =0.054). PD-0332991 shows promising biologic activity in ovarian cancer cell lines. Assessment of Rb and p16 expression may help select patients most likely to benefit from CDK4/6 inhibition in ovarian cancer. Gene expression of 40 individual ovarian cell lines relative to an ovarian cell line reference mix containing equal amounts of 41 ovarian cell lines (including OCC-1 which was later identified as originating from mouse). The expression data was correllated with cell line growth response to CDK 4/6 inhibitor PD-0332991 to identify genes associated with drug sensitivity and resistance.
2011-01-22 | E-GEOD-26805 | biostudies-arrayexpress
Project description:Breast cancer is a heterogeneous disease comprised of at least five major subtypes. Luminal subtype tumors confer a more favourable patient prognosis, which is in part, attributed to the Estrogen Receptor-alpha (ER) positivity and anti-hormone responsiveness of these tumors. Expression of the forkhead box transcription factor, FOXA1, also correlates with the luminal subtype and patient survival, but is present in a subset of ER-negative tumors. Similarly, FOXA1 is consistently expressed in luminal breast cancer cell lines even in the absence of ER. In contrast, basal breast cancer cell lines do not express FOXA1, and loss of FOXA1 in luminal cells increases migration and invasion, characteristics of the basal subtype. To delineate an ER-independent role for FOXA1 in maintaining the luminal phenotype, and hence a more favourable prognosis, we performed cDNA microarray analyses on luminal FOXA1-positive, ER-positive (MCF7, T47D) and FOXA1-positive, ER-negative (MDA-MB-453, SKBR3) cell lines in the presence or absence of transient FOXA1 silencing. This resulted in three FOXA1 transcriptomes: (1) a luminal-signature (consistent across cell lines), (2) an ER-positive signature (restricted to MCF7 and T47D) and (3) an ER-negative signature (restricted to MDA-MB-453 and SKBR3). Use of Gene Set Enrichment Analyses (GSEA) as a phenotyping tool revealed that FOXA1 silencing resulted in a transcriptome shift from luminal to basal gene expression signatures. FOXA1 binds to both luminal and basal genes within luminal breast cancer cells, suggesting that it not only transactivates luminal genes, but also represses basal-associated genes. From these results we conclude that FOXA1 controls plasticity between basal and luminal cells, playing a dominant role in repressing the basal phenotype, and thus tumor aggressiveness, in luminal breast cancer cells. Although it has been proposed that FOXA1-targeting agents may be useful for treating luminal tumors, these data suggest that this approach may promote transitions toward a more aggressive cancer. FOXA1 siRNA treated breast cell lines compared directly to nonspecific siRNA treated cell lines using Agilent 4X44 microarrays.
2012-03-09 | E-GEOD-31003 | biostudies-arrayexpress
Project description:Overexpression of heat shock proteins (HSPs), especially the major stress-inducible 72 kDa heat shock protein 70 (Hsp70), in malignant tumor cells is associated with therapeutic resistance. The heightened metabolic demand in tumor cells (Warburg effect) increases lactate dehydrogenase (LDH) activity and the corresponding increase in lactate concentrations promotes malignancy. Herein, we assessed the co-regulation of LDH and the heat shock response and its link to radiation resistance in B16F10 murine melanoma cells and LS174T human colorectal adenocarcinoma cells. Inhibition of LDHA/B by oxamate or GNE-140, significantly diminishes the expression of Hsp90, Hsp70 and Hsp27 in the cytosol. Diminished expression was also observed in LDHA/B double knockout (LDH-/-) cells. An increased production of reactive oxygen species (ROS) induced by a faster growth rate in wild type (WT) vs LDH-/- cells contributes to increased cytosolic HSP levels in WT cells. LDH-/- cells exhibit a lower density of membrane Hsp70 expression than WT cells and a decreased presence of the tumor-specific, Hsp70 anchoring glycosphingolipid Gb3 on the cell surface which could be attributed to an altered lipid metabolism mediated by the LDH knockout. Functionally, a double knockout of LDHA/B results in a generalized reduction in expression of HSPs in tumor cells and significantly increases radiosensitivity which is associated with a G2/M arrest. In summary, we demonstrate that pharmacological targeting of the lactate/pyruvate metabolism breaks radioresistance by impairing the stress response.
2022-02-17 | PXD026078 | Pride
Project description:Next Generation Sequencing of Unmethylated Alu (NSUMA) interrogation of more than 130,000 individual Alus for differential methylation with concomitant analysis of copy number variations applied to the study of hypomethylation in colorectal cancer. normal colon tissues, matched primary tumors, and colon derived cell lines
2015-09-08 | E-GEOD-72750 | biostudies-arrayexpress
Project description:RNA expression patterns of liver cell lines were compared to those of liver tumors to determine the suitability of cell lines as a model for drug development studies. The cell lines appear to recapitulate liver tumors. Gene expression of 20 individual liver cell lines relative to a liver cell line reference mix containing equal amounts of 19 liver cell lines. The expression data was correllated with expression in liver tumors.
2012-02-15 | E-GEOD-35818 | biostudies-arrayexpress
Project description:Sexual reproduction of Toxoplasma gondii, which is restricted to the small intestine of felids, is sparsely documented in studies involving domestic cats, which also raises ethical concerns. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites, as revealed by mass spectrometry-based proteomic analyses of the parasites.
2023-09-16 | PXD039400 | Pride
Project description:Viewing the scarce amount of protein material coming from the bacterial pathogen in infection models and despite the availability of contemporary, highly sensitive and fast scanning mass spectrometers, the power requirement still not suffices to study the host and pathogen proteomes simultaneously. In the present work we aimed to establish a DIA mass spectrometry workflow for improving the protein identification and quantification of LC-MS/MS, in Salmonella infected epithelial cells, therefore enabling simultaneous host and pathogen protein expression profiling at different time post infection.
2023-07-29 | PXD019863 | Pride
Project description:Tendons and ligaments are important biological structures in both humans and animals. They are part of dense connective tissue and are crucial to the functioning of the musculoskeletal system. However, they are commonly damaged due to age-related wear and tear, trauma or sports related incidents, which can lead to severe immobility for the individual and can lead to injury of other tissues and development of degenerative joint disease such as osteoarthritis. Tissue engineering can offer great potential in the treatment of tendon and ligament injury by seeking a biological replacement with fully regenerated autologenous tissue. This approach commonly involves an artificial ECM (scaffold) on which cell can proliferate and differentiate with subsequent new tissue generation. Fibrin is a natural scaffold with no expected toxic degradation or inflammatory reaction and can be used as an autologous scaffold for fibroblast from connective tissue to create a three dimensional structure. The purpose of this study was to compare the proteomic differences between native tendon, ligament and 3D tissue engineered tendon and ligament fibrin constructs.
2016-06-27 | PXD003094 | Pride
Project description:CpG 1826 binds to Toll-like receptor (TLR)9, whereas influenza virus PR8 activates pDC via TLR7. Differential stimulation of pDCs is expected to result in unique activation mechanism(s) leading to a different phenotypically and functionally matured pDC; We used microarrays to detail the global programme of gene expression underlying the maturation process of pDC activated with CpG 1826 and influenza virus PR8. We identified a distinct expression profile of upregulated immunomediators. Experiment Overall Design: Sorted pDCs were cultured for 1h and 4hs in medium control or with 5 µg/ml CpG 1826 or 300 HAU/ml purified influenza A/PR/8 virus. The first experiment (e1) included pDC in media and stimulated with CpG for 4h. In two other independent experimental batches (e2 and e3), we obtained samples of sorted pDC cultured in medium alone (med), and with CpG or PR8 (flu) for 1h and 4h. RNA extraction was performed using the RNeasy Kit (Qiagen) and hybridization on Affymetrix microarrays was performed using standard protocols. We sought to obtain homogeneous populations of pDCs at different time points under defined activation conditions in order to decipher the temporal resolution of expression profiles during the process of their maturation.
2008-06-15 | E-GEOD-7831 | biostudies-arrayexpress