STAT3 knockdown during transformation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE64536 | GEO | 2015/06/01
SECONDARY ACCESSION(S): PRJNA271263
REPOSITORIES: GEO
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Project description:We performed DNase-seq to study the dynamic genome-wide chromatin accessibility during MCF10A-ER-Src cell transformation.
2017-07-03 | GSE100255 | GEO
Project description:We performed ChIP-seq for histone modifications to map chromatin status and dynamics during MCF10A-ER-Src cell transformation.
2017-07-03 | GSE100257 | GEO
Project description:We performed RNA-seq to examine RNA expression profiles during MCF10A-ER-Src cell transformation and upon knockdowns of transcription factors
2017-07-03 | GSE100258 | GEO
Project description:We applied ribosome profiling and RNA sequencing to examine gene expression regulation during oncogenic cell transformation. One model involves normal mammary epithelial cells (MCF10A) containing ER-Src. Treatment of such cells with tamoxifen rapidly induces Src, thereby making it possible to kinetically follow the transition between normal and transformed cells. The other model consists of three isogenic cell lines derived from primary fibroblasts in a serial manner (Hahn et al., 1999). EH cell is immortalized by overexpression of telomerase (hTERT), and exhibits normal fibroblast morphology. EL cell expresses hTERT along with both large and small T antigens of Simian virus 40, and it displays an altered morphology but is not transformed. ELR cell expresses hTERT, T antigens, and an oncogenic derivative of Ras (H-RasV12).
2015-11-13 | GSE65885 | GEO
Project description:Purpose: The goal of this study is to examine gene expression regulation at the transcriptional and translational levels in response to various forms of nutrient deprivation, and whether there are differences between isogenic transformed and non-transformed cells. Mehods: We apply high-throughput sequencing of ribosome footprints (ribosome profiling) and poly(A) RNA (RNA sequencing) in an isogenic pair of transformed (tamoxifen-treated) and non-transformed (ethanol control) MCF10A-ER-Src cells subjected to the metabolic stresses that differentially affect global protein synthesis (Figure 1): deprivation of glutamine (for 30min and 4 hours), glucose (4hours), cysteine/cystine (4hours) or leucine/isoleucine/valine (brach-chain aminoacids - BCAA) (4hours). The same experiments were also performed in transformed ER-Src MCF10A treated with torin1 (500nM) for 4 hours. Results: Genome-wide translational profiling of glutamine deprived ER-Src MCF10A cells (for 30 minutes) shows increased translation of uORFs-containing mRNAs and down-regulation of ribosomal protein mRNAs, which is followed by increased translation and transcription of cytokine and inflammatory mRNAs (after 4 hours of glutamine deprivation). The transcription and translation of inflammatory and cytokine mRNAs is also stimulated in response to 4 hours deprivation of glucose, cysteine/cystine and BCAA, with the extent of stimulation correlating with the i) decrease in global protein synthesis and ii) down-regulation of all translationally-repressed mRNAs or ribosomal protein mRNAs. Conclusions: Pro-inflammatory gene expression is associated with translational repression in response to short-term nutrient deprivation.
2018-07-01 | GSE114794 | GEO
Project description:Characterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage.
2014-06-11 | GSE58359 | GEO
Project description:DNase-seq during MCF10A-ER-Src cell transformation
| PRJNA391165 | ENA
Project description:Characterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage. Examination of gene expression by RNAseq in two conditions in biological replicates.
2014-06-11 | E-GEOD-58359 | biostudies-arrayexpress
Project description:We profile the binding of Steroid Receptor Co-activator (SRC1) in LY2 cells, a tamoxifen-resistant cell line, in the presence and absence of tamoxifen using ChIP-sequencing technology. The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid-independent tumour. The p160 steroid coactivataor protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors, drives this tumour adaptability. Here, using discovery studies, we identify ADAM22, a non-protease member of the ADAMs family, as a direct, ER-independent target of SRC-1. Molecular, cellular and in vivo studies confirmed SRC-1 as a regulator of ADAM22. At a functional level, a role for ADAM22 in cellular migration and differentiation was observed. In vivo data from a mouse xenograft model indicated that ADAM22 expression was higher in 4-OHT-treated endocrine-resistant tumours than in tumours derived from isogenic, sensitive cells. Furthermore, in breast cancer patients, ADAM22 expression is an independent predictor of poor disease free survival. SRC-1 can function as a molecular switch which converts a steroid-responsive tumour to a steroid-resistant tumour. The ER-independent SRC-1 target ADAM22 is a potential drug target and a companion predictive biomarker in the treatment of endocrine-resistant breast cancer. Examination of SRC-1 binding in LY2 cells in the presence or absence of tamoxifen treatment. 2 replicates each.
2011-11-01 | E-GEOD-28987 | biostudies-arrayexpress
Project description:The agonistic/antagonistic bio-character of selective estrogen receptor modulators (SERMs) can have therapeutic advantages, particularly in the case of premenopausal breast cancers. Although the contradictory effects of these modulators have been studied in terms of cross-talk between estrogen receptor (ER)-coactivator dynamics and growth factor signaling, the molecular basis of these mechanisms is still obscure. We demonstrate here an unidentified series of regulatory mechanisms controlling cofactor dynamics on ER and SERM function whose activities require F-box protein 22 (Fbxo22). Skp, Cullin, F-box containing complex (SCF)Fbxo22 ubiquitylates lysine demethylase 4B (KDM4B) complexed with tamoxifen-bound ER, whose degradation releases steroid receptor coactivator (SRC) from ER. Depletion of Fbxo22 results in ER-dependent transcriptional activation via transactivation function 1 (AF1) function even in the presence of SERMs. In living cells, tamoxifen releases SRC and KDM4B from ER in a Fbxo22-dependent manner. SRC release by tamoxifen requires Fbxo22 on almost all ER-SRC-bound enhancer/promoters. Tamoxifen fails to prevent growth of Fbxo22-depleted ER-positive breast cancers both in vitro and in vivo. Clinically, a low level of Fbxo22 in tumor tissues predicts a poorer outcome in ER-positive/Human Epidermal Growth Factor Receptor Type 2 (HER-2)-negative breast cancers with high hazard ratios independently of other markers such as Ki-67 and node status. We propose that the level of Fbxo22 in tumor tissues defines a new subclass of ER-positive breast cancers for which patients SCFFbxo22-mediated KDM4B degradation can be a therapeutic target by the next generation of SERMs. We carried out the analysis using MCF-7 and Fbxo22-depleted MCF-7 cells. Cells were estrogen-starved for 72 hrs and subsequently stimulated for 2 hrs by E2 (10 nM) or E2 plus TAM. As a result, we identified a total of 12,645 and 23,216 enriched ER peaks in MCF-7 and Fbxo22-depleted MCF-7cells, respectively, in cells treated with E2, and 26,751 and 19,924 enriched ER peaks in MCF-7 and Fbxo22-depleted MCF-7cells, respectively, in cells treated with E2 plus 4-OHT.
2018-12-26 | GSE119702 | GEO