Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa in DMSO or medium with low LDL

ABSTRACT: Expression data from HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa treated with DMSO or medium with low LDL To determine which genes respond first to low concentrations of V-ATPase inhibition, we treated HeLa cells with two different V-ATPase inhibitors, bafilomycin and phenylsalicylihalamide (LX1077) at concentrations that slow cell growth by only 20%. To identify genes responding to expected effects of inhibiting the V-ATPase, expression data from inhibiting the V-ATPase was compared to that of chelating iron or incubating cells in medium with low LDL. We used microarrays to detail the global programme of gene expression in HeLa cells at 6, 12 & 24 hours culture in the presence of V-ATPase inhibitors. For each drug treatment, control cells were incubated at the same time with the same concentration of DMSO used as carrier for the drugs. HeLa cells were also treated with the iron chelator, desoxiferamine for 6 or 12 hours or with medium with low LDL for 12 hours to identify genes that respond to low iron or low cholesterol. Each timepoint and each treatment has two independent replicates. Experimental samples were compared to control samples grown on the same day.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Roth

PROVIDER: E-GEOD-16870 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

Straud Sarah S Zubovych Iryna I De Brabander Jef K JK Roth Michael G MG

PloS one 20100716 7

Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant ...[more]

PMID: 20661293

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Project description:Gene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes. Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation. 58 lung adenocarcinoma and 58 adjacent non-tumor lung fresh frozen tissues were macrodissected, and total RNA was isolated to be analyzed using the Illumina HumanWG-6 v3.0 expression beadchip.

Dataset Information

HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa in DMSO or medium with low LDL

Publications

Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

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