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Series GSE13476 Query DataSets for GSE13476
Status Public on Jan 30, 2009
Title Tamoxifen induces expression of immune-response related genes in cultured NHMEC
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Administration of tamoxifen (TAM) as breast cancer adjuvant therapy is associated with a 50% reduction in breast cancer risk and an increase in endometrial cancer risk. To investigate underlying mechanisms, we documented TAM-induced gene expression changes in cultured normal human mammary epithelial cell (NHMEC) strains (numbered 5, 16 and 40) established from tissue taken at reduction mammoplasty from three different individuals. Cells exposed to 0 and 10 uM TAM for 48 hours were evaluated for survival, TAM-DNA adduct formation by TAM-DNA chemiluminescence immunoassay (CIA), and gene expression changes using DNA-oligonucleotide microarray and real time reverse transcriptase-PCR (RT-PCR). At 48 hr, cells exposed to 10 uM TAM were 78% viable, respectively, and there were no measurable TAM-DNA adducts (limit of detection [LOD] = 0.3 adducts/10^8 nucleotides). For microarray analysis, RNA was extracted from cells exposed on three occasions to 10 uM TAM and the corresponding oligonucleotide probes were labeled with fluorescent dyes and hybridized to NCI microarrays (>20,000 human genes). Expression changes of > 3-fold were considered significant, and by these criteria, thirteen genes were up-regulated and one was down-related in NHMEC strain 16, seventeen genes were up-regulated in strain 05, and eleven genes were up-regulated in strain and 40. Elements that were up-regulated in all three cell strains included several interferon-induced genes (IFITM1, IFIT1, IFNA1, MXI and GIP3), and a potassium ion channel (KCNJ1). No significant expression changes were found for genes related to estrogen or xenobiotic metabolism. RT-PCR revealed TAM-induced up-regulation of the five genes of interest, and interferon รก (IFNA1), in all three NHMEC strains, with the exception of GIP3 and MX1, which were unchanged in strain 40. The magnitude of TAM-induced up-regulation ranked: strain 16 > strain 05> strain 40. The consistent induction of interferon-related genes in all three NHMEC strains suggests that, in addition to hormonal effects, TAM exposure may enhance immune response, through interferon induction, in normal breast tissue.
 
Overall design RNA was extracted from three cell strains (NHMEC 98016, 98040 and 99005) and exposed on three separate occasions to 10 uM TAM. Comparisons were made using 16 arrays with 8 dye swaps for cell strain NHMEC 99005, 9 arrays with 4 dye swaps for NHMEC 98016, and 12 arrays with 6 dye swaps for NHMEC 98040.
 
Citation(s) 19155303
Submission date Nov 05, 2008
Last update date Jan 17, 2013
Contact name Ofelia Ana Olivero
E-mail(s) oliveroo@exchange.nih.gov
Phone 3014357843
Organization name NCI-CCR-
Department CDI
Lab LCBG
Street address 37 Convent Dr-MSC 4255
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL1528 NCI/ATC Hs-OperonV2
Samples (37)
GSM339728 NHMEC 98016 - replicate 8 - mAdbID:45997
GSM339729 NHMEC 98016 - dye swap - replicate 9 - mAdbID:46000
GSM339730 NHMEC 98016 - replicate 5 - mAdbID:46071
Relations
BioProject PRJNA110153

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Supplementary file Size Download File type/resource
GSE13476_RAW.tar 70.4 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table
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