Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription profiling by array of human MCF7 breast cancer cells to study the acquisition of resistance to long term estrogen deprivation (LTED) on an aromatase inhibitor (AI)

ABSTRACT: The human oestrogen-positive breast cancer cell line MCF7 was cultured in phenol red-free RPMI medium supplemented with 10% fetal bovine serum, 10mg/ml insulin and 1nM estradiol (E2) and was referred to as wild-type MCF7. The wt-MCF7 cells were passaged weekly and medium was replenished every two to three days. To model acquisition of resistance to long term estrogen deprivation (LTED) on an aromatase inhibitor (AI), wt-MCF7 cells were cultured in phenol red-free RPMI medium supplemented with 10% dextran charcoal-stripped bovine serum (DCC) and 10mg/ml insulin. RNA was extracted from the LTED monolayers using RNeasy columns (Qiagen) according to manufacturer's protocol. RNA amplification, labeling and hybridization on HumanWG-6 v3 Expression BeadChips were performed according to the manufacturer's instructions (http://www.illumina.com) to assess changes in gene expression during adaptation to LTED.

ORGANISM(S): Homo sapiens

SUBMITTER: Ghazoui Zara

PROVIDER: S-ECPF-MTAB-922 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling by array of human estrogen receptor positive breast cancer cell lines after long-term estrogen deprivation

Project description:Hyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer. A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. We used gene expression microarrays to identify genes and pathways that are commonly dysregulated in ER+ cell lines with acquired hormone-independent growth. MCF-7, ZR75-1, MDA-361, and HCC-1428 ER+, estrogen-responsive breast cancer cells were cultured under hormone-depleted conditions (10% DCC-FBS) for several months until sustainable hormone-independent cell populations emerged. Parental and long-term estrogen-deprived (LTED) cells were treated with 10% dextran-coated charcoal-treated fetal bovine serum (DCC-FBS) x 24 hrs prior to RNA harvest for array analysis.

| S-ECPF-GEOD-19639 | biostudies-other

Transcription profiling by array of human MCF7 cell lines to investigate GDNF-RET signaling as a target in aromatase inhibitor resistant breast cancers

Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).

| S-ECPF-MEXP-3662 | biostudies-other

Expression data from MCF7 and BT474 cell lines after long term estrogen deprivation culture

Project description:MCF7 and BT474 cell lines were exposed to LTED culture for 0 and 2 days, 6 weeks and 10 months and monitored for changes in gene expression

2013-10-02 | GSE50820 | GEO

Transcription profiling of human estrogen receptor positive MCF7 cells stably transfected with aromatase gene treated with testosterone, 17 B-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an anti-estrogen (tamoxifen)

Project description:Anti-estrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. In order to investigate the effects of these drugs on gene expression in breast cancer cells, we treated estrogen receptor-positive MCF-7 cells, stably transfected with the aromatase gene (known as MCF-7aro cells), with testosterone, 17β-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an anti-estrogen (tamoxifen). Microarray analyses using Affymetrix Human Genome U133A GeneChips were carried out using total RNA isolated from the control and treated cells. When comparing the effect of each inhibitor on gene expression we observe that letrozole and anastrozole are more similar in terms of the genes they affect, compared to treatment with tamoxifen. The results of this study provide us with a better understanding of the actions of both aromatase inhibitors and anti-estrogens at the molecular level. We believe that the results of this study serve as the first step in identifying unique expression patterns following drug treatment, and that this will ultimately be useful in customizing patient treatment strategies for estrogen-dependent breast cancer. The data presented here have been processed using the R-Project Bioconductor statistical tools package using the affy library. The following were applied: RMA background correction, pmonly probe-level correction, quantile normalization, avgdiff summary method. Raw data is provided in the form of .CEL files.

| S-ECPF-GEOD-2225 | biostudies-other

Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer.

Project description:BackgroundThe tamoxifen metabolite, Z-endoxifen, demonstrated promising antitumor activity in endocrine-resistant estrogen receptor-positive (ER+) breast cancer. We compared the antitumor activity of Z-endoxifen with tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), as well as with tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus in a letrozole-resistant MCF7 model (MCF7LR).MethodsMCF7AC1 tumor-bearing mice were randomized to control (no drug), letrozole (10 μg/day), tamoxifen (500 μg/day), or Z-endoxifen (25 and 75 mg/kg). Treatment in the letrozole arm was continued until resistance developed. MCF7LR tumor-bearing mice were then randomized to Z-endoxifen (50 mg/kg) or tamoxifen for 4 weeks and tumors harvested for microarray and immunohistochemistry analysis. The antitumor activity of Z-endoxifen in the MCF7LR tumors was further compared in a second in vivo study with exemestane, exemestane plus everolimus, and fulvestrant.ResultsIn the MCF7AC1 tumors, both Z-endoxifen doses were significantly superior to control and tamoxifen in reducing tumor volumes at 4 weeks. Additionally, the 75 mg/kg Z-endoxifen dose was additionally superior to letrozole. Prolonged letrozole exposure resulted in resistance at 25 weeks. In MCF7LR tumor-bearing mice, Z-endoxifen significantly reduced tumor volumes compared to tamoxifen, letrozole, and exemestane, with no significant differences compared to exemestane plus everolimus and fulvestrant. Additionally, compared to tamoxifen, Z-endoxifen markedly inhibited ERα target genes, Ki67 and Akt expression in vivo.ConclusionIn endocrine-sensitive and letrozole-resistant breast tumors, Z-endoxifen results in robust antitumor and antiestrogenic activity compared to tamoxifen and aromatase inhibitor monotherapy. These data support the ongoing development of Z-endoxifen.

| S-EPMC7238733 | biostudies-literature

Expression data from MCF7 and BT474 cell lines after long term estrogen deprivation culture

Project description:MCF7 and BT474 cell lines were exposed to LTED culture for 0 and 2 days, 6 weeks and 10 months and monitored for changes in gene expression MCF7 0 days vs 2 days, 6 weeks and 10 months, BT474 0 days vs 2 days, 6 weeks and 10 months

2013-10-02 | E-GEOD-50820 | biostudies-arrayexpress

Transcription profiling by array of aromatase-inhibitor-resistant breast cancer cell lines derived from T-47D to identify the genes related to aromatase-inhibitor-resistance

Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D.

| S-ECPF-MTAB-1933 | biostudies-other

Dynamic changes during adaptation to estrogen deprivation in MCF7 cell line

Project description:Endocrine therapies targeting the proliferative effect of 17β-estradiol (17βE2) through estrogen receptor α (ERα) are the most effective systemic treatment of ERα-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through a molecular mechanism that is not yet fully understood. The long-term estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors (AIs) in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ERα. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were influenced by transcription factors known to be involved in acquired resistance or cell proliferation (e.g. IRF1 and E2F1, respectively) but, notably, not by canonical ERα transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)- to pS167-ERα were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ERα-negative status, early response to letrozole and recurrence after tamoxifen treatment. This study proposes a mechanism for acquired resistance to estrogen deprivation that is coordinated across biological levels and independent of canonical ERα function. LTED (long term estrogen deprived) cell line was generated from MCF-7 cells by long-term culture under estrogen deprivated conditions. And RNA samples were obtained after 3, 15, 30, 90, 120, 150 and 180 days.

| S-ECPF-GEOD-20361 | biostudies-other

Effect of aromatase inhibitor (AI) treatment on gene expression of breast cancer [tissueseq]

Project description:To investigate the expression profiling of estrogen receptor positive breast cancer after AI treatment, we obtained tumor samples from breast cancer patients receiving adjuvant AI treatment, then performed RNA sequencing and gene expression profiling analysis for 14 different breast tumor samples.

2022-10-11 | GSE206199 | GEO

Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer.

Project description:Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.

| S-EPMC9652412 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data