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Series GSE50694 Query DataSets for GSE50694
Status Public on Jan 16, 2014
Title Endocrine response in invasive lobular carcinoma is characterized by unique estrogen-mediated gene expression and de novo tamoxifen resistance (SUM44)
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer that is frequently associated with favorable outcomes, as ~90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that ILC patients receiving adjuvant endocrine therapy may not benefit from improved outcomes versus other breast cancer patients. Based on these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome in vitro via gene expression microarray analyses and ER ChIP-Seq. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. Response to endocrine therapy was also examined in ILC cell lines. We identified 915 genes that were uniquely E2-regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also regulated in vivo in HCI-013. We observed that MM134 were de novo tamoxifen resistant, and were induced to grow by 4-hydroxytamoxifen, as well as other anti-estrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required FGFR1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.
Overall design Cells were hormone deprived by replacing growth medium with IMEM+2% charcoal stripped serum for 3 days. Following deprivation, cells were treated for 3 or 24 hours with 1nM E2 or vehicle (0.01% EtOH) in biological quadruplicate. Following treatment, cells were lysed and RNA was harvested using the Illustra RNAspin Mini kit (GE Health). cRNA synthesis and labeling was performed using the Ambion MessageAmp Premier Kit (Life Technologies), and cRNA was hybridized to U133A 2.0 arrays (Affymetrix, Santa Clara, CA). cRNA synthesis and labeling, hybridization, and scanning were performed by the University of Pittsburgh Cancer Biomarkers Facility.
Contributor(s) Sikora MJ, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, Davidson NE, Dabbs DJ, Welm AL, Oesterreich S
Citation(s) 24425047
Submission date Sep 09, 2013
Last update date Dec 06, 2018
Contact name Uma Chandran
Phone 412-648-9326
Organization name University of Pittsburgh
Department BioMedical Informatics
Street address 5150 Center Ave
City Pittsburgh
State/province PA
ZIP/Postal code 15232
Country USA
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (20)
GSM1226542 SUM44 0hr A
GSM1226543 SUM44 0hr B
GSM1226544 SUM44 0hr C
This SubSeries is part of SuperSeries:
GSE50695 Endocrine response in invasive lobular carcinoma is characterized by unique estrogen-mediated gene expression and de novo tamoxifen resistance
BioProject PRJNA218517

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Supplementary file Size Download File type/resource
GSE50694_RAW.tar 40.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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