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SRX796259: GSM1558525: Paired-end_BRCA_rep1; Mus musculus; RNA-Seq
1 ILLUMINA (Illumina HiSeq 2000) run: 60.4M spots, 6.2G bases, 3.9Gb downloads

Submitted by: Gene Expression Omnibus (GEO)
Study: Comparison of tamoxifen and letrozole response in mammary preneoplasia of ER and aromatase over-expressing mice defines an immune-associated gene signature linked to tamoxifen resistance
show Abstracthide Abstract
To investigate response or resistance to endocrine therapy, mice with targeted over-expression of Esr1 or CYP19A1 to mammary epithelial cells were employed, representing two direct pathophysiological interventions in estrogen pathway signaling. Both Esr1 and CYP19A1 over-expressing mice responded to letrozole with reduced HAN prevalence and decreased mammary epithelial cell proliferation. CYP19A1 over-expressing mice were tamoxifen-sensitive but Esr1 over-expressing mice were tamoxifen-resistant. Increased ER expression occurred with tamoxifen resistance but no consistent changes in progesterone receptor, pSTAT3, pSTAT5, cyclin D1 or cyclin E levels in association with response or resistance was found. RNA-seq was employed to seek a transcriptome predictive of tamoxifen resistance using these models and a second tamoxifen-resistant model, BRCA1 deficient/Trp53 haploinsufficient mice. Sixty-eight genes associated with immune system processing were upregulated in tamoxifen-resistant Esr1 and Brca1 deficient mice whereas genes related to aromatic compound metabolic process were upregulated in tamoxifen-sensitive CYP19A1 mice. Interferon Regulatory Factor 7 was identified as a key transcription factor regulating these 68 immune processing genes. Two loci encoding novel transcripts with high homology to human IGLL1 were uniquely upregulated in the tamoxifen-resistant models. Letrozole proved to be a successful alternative to tamoxifen. Further study of transcriptional changes associated with tamoxifen resistance including immune-related genes could expand our mechanistic understanding and lead to biomarkers predictive of escape or response to endocrine therapies. Overall design: Single- and paired-end mRNA-seq with WT, Esr1 over-expressing (CERM, tetracycline-operator(tet-op)-Esr1MMTV-rtTA), CYP19A1 over-expressing (AROM, tet-op-CYP19A1MMTV-rtTA) and Brca1 KO (BRCA, Brca1fl11/fl11/MMTV-Cre/p53+/- ) mice
Sample: Paired-end_BRCA_rep1
SAMN03252726 • SRS779713 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina HiSeq 2000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Total RNA was extracted from homogenized mammary glands using Trizol (Invitrogen) and 300μl chloroform (Thermo Fisher Scientific, Waltham, MA) for phase separation, precipitated with 650μl isopropanol (Thermo Fisher Scientific) and purified using an RNeasy Plus Mini Kit (Qiagen, Valencia, CA). Polyadenylated (polyA) RNA was isolated from 1ug total RNA and converted to cDNA using SuperScript II (Invitrogen). A TruSeq RNA Sample Preparation Kit (Illumina, San Diego, CA) was used to generate sequencing libraries according to the manufacturer’s instructions. Libraries were independently sequenced by both single- and paired-end methods using HiSeq 2000 (Illumina).
Experiment attributes:
GEO Accession: GSM1558525
Links:
External link:
Runs: 1 run, 60.4M spots, 6.2G bases, 3.9Gb
Run# of Spots# of BasesSizePublished
SRR169343260,366,3596.2G3.9Gb2014-12-08

ID:
1139815

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