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Series GSE76608 Query DataSets for GSE76608
Status Public on May 26, 2016
Title Expression profiling of MCF-7 cells with 10nM treatment of TCDD
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). L-Type Amino Acid Transporter 1 (LAT1) is a leucine uptake transporter that is overexpressed in cancer. The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport. Overlapping the TCDD-RNA-Seq dataset in this report with a published TCDD-ChIP-seq dataset identified that LAT1 was a direct TCDD/AHR gene target. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR. TCDD-stimulated increases in LAT1 mRNA was also inhibited by the AHR antagonist CH-223191. Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD. In MDA-MB-231 cells, which exhibit high levels of endogenous AHR activity, the levels of endogenous LAT1 mRNA and protein were reduced in response to knockdown of AHR with AHR-siRNA. The regulation of LAT1 by AHR stimulated MDA-MB-231 proliferation. Collectively, these findings have provided a deeper mechanistic understanding of extrinsic and intrinsic regulation of LAT1 by AHR.
Overall design Expression profiling of four replicates of MCF-7 cells treated with 10nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq
Contributor(s) Denvir J, Salisbury TB, Tomblin JK, Arthur S, Primerano DA, Chaudhry AR, Fan J
Citation(s) 26944194
Submission date Jan 06, 2016
Last update date May 15, 2019
Contact name James Denvir
Organization name Marshall University School of Medicine
Department Biochemistry and Microbiology
Lab Genomics and Bioinformatics Core Facility
Street address One John Marshall Drive
City Huntington
State/province WV
ZIP/Postal code 25755
Country USA
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (8)
GSM2028919 MCF-7 cells treated with DMSO, replicate 1
GSM2028920 MCF-7 cells treated with DMSO, replicate 2
GSM2028921 MCF-7 cells treated with DMSO, replicate 3
This SubSeries is part of SuperSeries:
GSE98515 Expression profiling of MCF-7 cells with treatment of TCDD
BioProject PRJNA308136
SRA SRP068163

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Supplementary file Size Download File type/resource
GSE76608_counts_10nM_TCDD.txt.gz 637.2 Kb (ftp)(http) TXT
GSE76608_normalized_counts_10nM_TCDD.txt.gz 1.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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