GEO DataSets

(Submitter supplied) Activation of the PI3K pathway in estrogen receptor α (ER)-positive (+) breast cancer is associated with reduced ER expression and activity, luminal B subtype, and poor outcome. PTEN is a negative regulator of the PI3K pathway typically lost in ER-negative (-) breast cancer. To clarify the effect of PTEN down-regulation on the response of ER+/HER2- breast cancer to endocrine therapy, we established reduced PTEN cell models using inducible knockdown. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9052

2 Samples

Download data: FPKM_TRACKING

(Submitter supplied) Phosphoinositide-3-kinase/protein-kinaseB/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling plays an important role in breast cancer (BC). Its interaction with estrogen receptor (ER) signalling becomes more complex and inter-dependent with acquired endocrine resistance. Targeting mTOR combined with endocrine therapy has shown clinical utility, however, a negative feedback-loop exists downstream of PI3K/AKT/mTOR. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

12 Samples

Download data: TXT

(Submitter supplied) Introduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option. Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor). Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach. Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

46 Samples

Download data: TXT

(Submitter supplied) To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

65 Samples

Download data: CEL

(Submitter supplied) To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

14 Samples

Download data: CEL, XLS

(Submitter supplied) To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

51 Samples

Download data: CEL, TXT

(Submitter supplied) Introduction Basal-like (BLCs) and epidermal growth factor receptor 2 overexpressing (HER2+) carcinomas are the subgroups of breast cancers which have the more aggressive clinical behavior. In contrast to HER2+ carcinomas, no targeted therapy is currently available for the treatment of patients with BLCs. In order to discover potential therapeutic targets, we searched for deregulated signaling pathways in human BLCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

23 Samples

Download data: CEL

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

24 Samples

Download data: CEL, CHP

(Submitter supplied) Background: Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30-40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

77 Samples

Download data: CEL, RDATA, TXT

(Submitter supplied) Purpose: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC): basal-like, ErbB2-like and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER)-positive subtypes has been inconsistent. Refinement of their molecular definition is therefore needed. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL96 GPL97 GPL570

741 Samples

Download data: CEL, RDATA, TXT

(Submitter supplied) A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. A kinome-wide siRNA screen identified a role for Insulin Receptor (InsR) in the hormone-independent growth of ER+ breast cancer cells We used gene expression microarrays to identify genes and pathways that are altered by insulin stimulation of ER+ MCF-7 human breast cancer cells.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13158

9 Samples

Download data: CEL, CHP

(Submitter supplied) RNA-sequencing analysis of RBP2 overexpressing MCF7 cell lines. RBP2 (also known as JARID1A), a member of the JARID1 family of histone H3 lysine K4 demethylases, has been considered to have an oncogenic potential in several cancer including breast cancer. Results provide insight into the transcriptional regulation of RBP2 in estrogen receptor positve breast cancer.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: TXT

(Submitter supplied) Purpose: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole was approved for treatment of ER+ advanced breast cancer, and other CDK4/6 inhibitors are being investigated in combination with different endocrine treatments. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

26 Samples

Download data: CEL

(Submitter supplied) First line treatment with AKT inhibitors combined with paclitaxel improves outcomes of metastatic TNBC, especially in tumors that harbor mutations in PTEN/PIK3CA/AKT1. In this work, we refine the composite response biomarker to AZD5363 in this setting, which is relevant to inform the clinical development of these drugs.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

9 Samples

Download data: TSV

(Submitter supplied) The overarching goal of this study was to explore the antitumor activity of Z-endoxifen, a tamoxifen metabolite, with first-line endocrine therapies tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), and with second-line endocrine therapies including tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus, in letrozole-resistant MCF7 model (MCF7LR) in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

11 Samples

Download data: CEL

(Submitter supplied) Purpose: To assess if NLK modulates ER target gene expression, we performed transcriptome sequencing following NLK inhibition or tamoxifen treatment in the BT483 or T47D-TamR cells under estrogen-deprived condition. Methods: BT483 and T47D-TamR cells were treated with NLK-specific siRNAs, or VX-702, or Tamoxifen under estrogen-deprived condition to examine the expression profile changes of ER target genes. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

11 Samples

Download data: TXT

(Submitter supplied) The transcription factor FOXM1 coordinates the expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We have previously shown that FOXM1 acts downstream of 14-3-3ζ signaling, which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering the resistance to endocrine treatments in estrogen receptor-positive (ER+) patients when tumor FOXM1 is high, has not been clearly defined. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL96

7 Samples

Download data: CEL

(Submitter supplied) Periodic fasting or modified fasting hold promise as strategies to enhance the activity of cancer treatments. We aimed at defining whether culture conditions that mimic the metabolic effects of fasting (1% serum and 0.5 g/L glucose) have an impact on the effects of tamoxifen, a broadly used selective estrogen receptor modulator, on the gene expression profile of MCF7 cells, a hormone receptor+ breast cancer cell line.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10332

16 Samples

Download data: TXT

(Submitter supplied) Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

864 Samples

Download data: TXT

(Submitter supplied) We performed ChIP seq experiment in MDA-MB-134 cell line in order to map the estrogen receptor alpha (ER) binding sites following the estrogen treatment in an ILC model. We have characterized the genome wide recruit of ER and scaned the binding sites for the presence of cofactor motifs. The binding peaks were also correlated to E2 regulated genes in this ILC model.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: BEDGRAPH