AIB1 dependent transcriptome in endocrine resistance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663934 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12658548_1.fastq.gz | Fastqsanger.gz | |||
| SRR12658548_2.fastq.gz | Fastqsanger.gz | |||
| SRR12658549_1.fastq.gz | Fastqsanger.gz | |||
| SRR12658549_2.fastq.gz | Fastqsanger.gz | |||
| SRR12658550_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: AIB1 expression is associated with disease progression in aromastase inhibitor (AI) treated patients in breast cancer. In order to identify genes aberrantly regulated by AIB1 in AI resistance, RNA-seq was carried out in endocrine resistant LetR cells and endocrine sensitive MCF7 cells +/- AIB1 under estrogen deprivation. Methods: RNA-seq was carried out in biological triplicate in MCF7 and LetR cells comparing NT (Scramble siRNA) cells versus cells depleted of AIB1 using a SMARTpool ON-TARGETplus siRNA. RNA was extracted using Qiagen RNeasy Kit and subjected to 100bp PE sequencing using the BGISEQ 500 platform. Briefly, clean reads were mapped to reference genome using Bowtie2 and gene expression was calculated with RSEM. Differentially expressed genes (DEGs) were detected with DEseq2. With the KEGG pathway analysis, the pathway functional enrichment was performed using phyper, a function of R. Results: 61 AIB1 differentially regulated genes were identified as unique to endocrine resistant tumor cells (logfc≥1.5; Padj≤0.05).MSigDB Oncogenic signature analysis of the 61 AIB1-regulated genes revealed enrichment in growth promoting endocrine resistance pathways including LTE2, RAF, ERBB2 and MEK. Conclusion: In the endocrine resistant setting, aberrant AIB1 expression regulates the expression of genes associated with growth factor signalling.
2020-12-30 | GSE158095 | GEO
Project description:The estrogen receptor alpha (ERa) drives the growth of two-thirds of all breast cancers. Endocrine therapy impinges on estrogen-induced ERa activation to block tumor growth. However, half of ERa-positive breast cancers are tolerant or acquire endocrine therapy resistance. Here we demonstrate that breast cancer cells undergo genome-wide reprogramming of their chromatin landscape, defined by epigenomic maps and chromatin openness, as they acquire resistance to endocrine therapy. This reveals a role for the Notch pathway while excluding classical ERa signaling. In agreement, blocking Notch signaling, using gamma-secretase inhibitors, or targeting its downstream gene PBX1 abrogates growth of endocrine therapy-resistant breast cancer cells. Moreover Notch signaling through PBX1 directs a transcriptional program predictive of tumor outcome and endocrine therapy response. Comparing histone modifications (H3K4me2 and H3K36me3), chromatin openness (FAIRE) and PBX1 binding between endocrine therapy sensitive MCF7 and resistant MCF7-LTED cells.
2013-05-01 | E-GEOD-37323 | biostudies-arrayexpress
Project description:Estrogen receptor alpha (ERα) expression in breast cancer is predictive of response to endocrine therapy, however resistance is common in ERα-positive tumors that over-express the growth factor receptor ERBB2. Even in the absence of estrogen, ERα can be activated by growth factors including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen, however the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ERα genomic targets, its cistrome, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERα cistrome specifically regulates genes found over-expressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that over-express ERBB2. These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα as opposed to blocking its estrogen responsiveness alone.
2010-12-29 | GSE26081 | GEO
Project description:The estrogen receptor alpha (ERa) drives the growth of two-thirds of all breast cancers. Endocrine therapy impinges on estrogen-induced ERa activation to block tumor growth. However, half of ERa-positive breast cancers are tolerant or acquire endocrine therapy resistance. Here we demonstrate that breast cancer cells undergo genome-wide reprogramming of their chromatin landscape, defined by epigenomic maps and chromatin openness, as they acquire resistance to endocrine therapy. This reveals a role for the Notch pathway while excluding classical ERa signaling. In agreement, blocking Notch signaling, using gamma-secretase inhibitors, or targeting its downstream gene PBX1 abrogates growth of endocrine therapy-resistant breast cancer cells. Moreover Notch signaling through PBX1 directs a transcriptional program predictive of tumor outcome and endocrine therapy response.
2013-05-01 | GSE37323 | GEO
Project description:Dataset containing micro-RNA expression profiles of breast cancers at the time of endocrine resistance. It has been used to correlate micro-RNA and mRNA expressions and to identify two distinctive phenotypes with different expression of micro-RNA gens. Please note that the tumor samples are clinically quite homogeneous: all are post-menopausal ER+ve breast cancers, endocrine treated and growing on treatment. The main purpose of collecting these data was not to compare transcriptional profiles with clinical parameters, but rather to use the micro-RNA expression profiles of these clinically homogeneous tumours for (i) identifying intrinsic subgroups within endocrine resistance and (ii) for relating micro-RNA and mRNA expressions. However, the relevant clinical data was also provided as Series supplementary file (ClinicalData_AL28Jan2014.xlsx).
2014-12-01 | GSE54496 | GEO
Project description:This experiment used RNA-Seq technology to explore gene expression in mouse Ngn3^GFP/+ [het] FACS sorted pancreatic cells at E15.5 (commited endocrine progenitor cells) and in Ngn3^GFP/GFP [null] at E15.5 (defective endocrine progenitor cells). This experiment is designed to understand the gene expression alteration in the endocrine lineage at different embryonic days. The aim is to understand both Ngn3 dependent and independent gene expression profiles so as to reveal the instructive signals that specfy the collective endocrine islet cell fate or specific islet cell type.
2015-10-01 | E-MTAB-3352 | biostudies-arrayexpress
Project description:Phenotypic plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies, including GRO-seq on enhancer landscapes, demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ER-alpha and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alters breast cancer transcriptional programs. Our functional studies in multiple biological systems support a coordinate role of GATA3 and AP1 in enhancer reprogramming that drives phenotypic plasticity to achieve endocrine resistance or cancer invasive progression. Thus, changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression
2019-05-24 | MSV000083857 | MassIVE
Project description:Resistance to endocrine therapy represents a major threat to patients with estrogen receptor α positive (ERα+) breast cancer. The development of resistance is mainly through activating E2F signaling. However, the mechanisms that govern E2F1 activity in these resistant cells remain poorly understood. Here, we identify Actin Gamma 1 Pseudogene 25 (AGPG) as a lncRNA whose expression is driven by epigenomic activation of enhancer in endocrine resistant breast cancer cells. High expression of AGPG is associated with poor survival of ERα+ breast cancer, especially in patients receiving endocrine therapy. Stable knockdown and overexpression of AGPG demonstrate that AGPG promotes endocrine resistance, cell cycle progression, cell proliferation in vitro and in vivo. AGPG functions by direct binding purine rich element binding protein α (PURα), a transcription factor repressing E2F1 signaling and sensitized ERα+ breast cancer cells to endocrine therapy. Via binding to the region responsible for PURα/E2F1 interaction in PURα protein, AGPG releases E2F1 from PURα, leading to activation of E2F1 signaling in ERα+ breast cancer cells. Clinically, E2F1 target genes are strongly correlated with AGPG and PURα expression. Thus, our study reveals AGPG as a promising biomarker and potential therapeutic target in breast cancer.
2023-07-12 | GSE218130 | GEO
Project description:*** This submission includes RNA data, with DNA files available under a different accession number*** Purpose: Endocrine therapy resistance remains the greatest challenge for treating hormone receptor positive breast cancer patients. We aim to identify molecular mechanisms underlying endocrine therapy resistance through in-depth genomic analysis of patient samples. Experimental Design: We collected tumors from 35 estrogen receptor positive breast cancer patients receiving endocrine therapy, of which 3 patients had intrinsic resistance and 19 patients developed acquired resistance. For each patient, multiple tumor specimens were collected during the course of treatment. We performed DNA whole exome sequencing and RNA sequencing on all tumor samples. DNA mutations, copy number alterations and RNA gene expression data were analyzed through supervised analyses comparing paired sensitive and resistant tumor samples to identify molecular features related to endocrine therapy resistance. Results: We identified mutations enriched in resistant tumors including ESR1 and GATA3. ESR1 D538G variant confers endocrine therapy resistance while E380Q variant confers hypersensitivity. We demonstrate that resistant tumors had distinct gene expression profiles and elevated signaling pathways including ER, HER2, GATA3, AKT, RAS and p63 signaling. Integrated analysis for individual patient highlighted the heterogeneity of endocrine therapy resistance mechanisms. Conclusions: Our results suggest that mechanisms underlying endocrine therapy resistance are highly heterogeneous with diverse changes in genomic and transcriptomic levels.
2022-09-01 | E-MTAB-9917 | biostudies-arrayexpress
Project description:Acquired resistance to endocrine therapy occurs with high frequency in patients with luminal breast cancer (LBC). We report here the establishment of four patient-derived xenograft models of LBC with acquired resistance in vivo to tamoxifen and estrogen deprivation. CEL files represent expresison data generated from 5 replicates (independent mice) of the following tumor models: HBCx22 (parental), HBCx22 TamR (tamoxifen-resistant), HBCx22 OvaR (ovariectomy-resistant), HBCx34 (parental), HBCx34 TamR (tamoxifen-resistant), HBCx34 OvaR (ovariectomy-resistant)
2014-07-09 | E-GEOD-55561 | biostudies-arrayexpress