Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Tempo-Seq targeted RNA sequencing of the HepaRG cell line treated with aflatoxin B1, benzo[a]pyrene, cyclosporin A, rotenone and thrichostatin A over a range of chemical concentrations and exposure time points

ABSTRACT: The experiment investigates the effects of five well-known chemicals on the transcriptome of the HepaRG cell line, a metabolically competent hepatic cell line. The cells were treated individually with an increasing concentrations of aflatoxin B1, benzo[a]pyrene, cyclosporine A, rotenone or trichostatin A at five exposure time points followed by targeted RNA-seq using TempO-Seq technology (the panel of human whole transcriptome). The aim of the study was to explore how and to what extent the point-of-departure (POD) obtained from an in vitro transcriptomics study varied as a function of exposure time.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Donatella Carpi

PROVIDER: E-MTAB-13168 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Breast cancer is a heterogeneous disease classified into 3 major subtypes based on the presence or absence of molecular markers for oestrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor-2 (Her2) . Hormone receptor-positive BC (ER+, PR+ and Her-2-), accounts for approximately 70% of patients. Patients with ER- BC account for approximately 30 % of all cases and commonly have a worse prognosis than ER+ patients (9). However, a significant proportion of ER- cases have good outcomes and could potentially benefit from a less aggressive therapy. Triple negative breast cancer (TNBC, ER-, PR- and Her-2-) accounts for approximately 15% of breast cancers and has the poorest outcomes. An hypoxic microenvironment is an important intrinsic component of solid tumours that can result in rapid proliferation of cancer cells and is associated with the lack of oxgyen and abnormal tumour blood vessels. Hypoxia stimulates the hypoxia inducible factor-1α (HIF-1α) that transactivates genes associated with angiogenesis, tumour growth, metastasis, metabolic reprogramming, and treatment resistance. HIF-1α is recognised to induce the expression of carbonic anhydrase IX (CAIX), an enzyme that has been attributed a central role in pH regulation and cancer progression and is particularly pronounced in peri necrotic tumour areas, high-grade BCs. The adaption to hypoxia is governed by multiple transcriptional and post-transcriptional changes in gene expression. Up to 1.5 % of the human genome is estimated to be transcriptionally responsive to hypoxia. Genes and pathways which have been identified as being responsive to hypoxia may have the potential to be used as prognostic or predictive markers, and furthermore, can help identify novel therapeutic targets. The aim of the present study was to gain a better understanding of the transcriptomic and protein pathways associated with CAIX in ER- BC to identify potential therapeutic targets against this aggressive phenotype.

Dataset Information

Tempo-Seq targeted RNA sequencing of the HepaRG cell line treated with aflatoxin B1, benzo[a]pyrene, cyclosporin A, rotenone and thrichostatin A over a range of chemical concentrations and exposure time points

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