Chromatin profile-based identification of a novel ER-positive breast cancer subgroup with reduced ER-responsive element accessibility
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PROVIDER: PRJNA918314 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen receptor (ER) signaling–dependent cancer cell growth is one of the major features of ER-positive breast cancer (BC). Inhibition of ER function is a standard and effective treatment for ER-positive tumors; however, ~20% of patients with ER-positive BC experience early or late recurrence. In this study, we examined intertumor heterogeneity from an epigenetic perspective based on the hypothesis that the intrinsic difference in epigenetic states around ER signaling pathway underlies endocrine therapy resistance. We profiled chromatin accessibility data from 42 BC samples, including 35 ER-positive human epidermal growth factor receptor 2 (HER2)-negative and 7 triple-negative tumors, identifying a subgroup of ER-positive BCs with a distinctive chromatin accessibility pattern including reduced accessibility to ER-responsive elements (EREs). The same subgroup was also observed in The Cancer Genome Atlas BC cohort. Despite the reduced accessibility to EREs, the expression of ER and potential ER target genes were not decreased in these tumors. Our findings highlight the existence of a subset of ER-positive BCs with unchanged ER expression but reduced EREs accessibility that cannot be distinguished by conventional immunostaining for ER. Future studies should determine whether these tumors are associated with resistance to endocrine therapy.
2023-01-09 | GSE222116 | GEO
Project description:To better characterize group IE like human breast cancer based on the gene profiles of estrogen actions through estrogen receptor alpha (ER alpha), we identified an ER alpha transcriptional regulatory network for cell cycle in silico. We used two datasets from cell line (Data 1) and clinical samples (Data 2), respectively. Analyses on Data 1 via trajectory clustering and Pathway-Express confirmed the significant estrogen effect on up-regulating cell cycle activities. The gene expression relationships between ER alpha and cell cycle genes were re-identified in Data 2 by three statistical methods – Galton-Pearson’s correlation coefficient, Student’s t-test and the coefficient of intrinsic dependence. They were mostly (56.09%)(46/82) re-confirmed by literature search. E2F1 was found to be the major ER alpha target in regulating cell cycle gene expressions (83.72%)(36/43) via suppressive mode. However, enhanced cell cycle progression via up-regulating some cell cycle genes was predicted in silico possibly involving E2F2, in part. Both tumorigenic and tumor suppressing activities indicated by this network were predicted. This network clearly provides a robust way for uncovering estrogen actions in an ER(+) subtype specific manner.
2009-07-24 | GSE17040 | GEO
Project description:Sonic Hedgehog subgroup medulloblastomas
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Project description:Impaired proinsulin processing is observed in both type 1 and type 2 diabetes. We have previously shown that reductions in endoplasmic reticulum (ER) calcium (Ca2+) in the pancreatic β cell arising from impaired activity of the Sarcoendoplasmic Reticulum Ca2+ ATPase (SERCA) pump are associated with increased proinsulin secretion. However, the mechanisms responsible for reduced proinsulin processing in the context of SERCA2 deficiency remain incompletely understood. To test this, we developed mice with β cell specific SERCA2 deletion (βS2KO mice) and S2KO INS1 cells. βS2KO mice exhibited age-dependent glucose intolerance and reduced glucose-stimulated insulin secretion without evidence of impaired insulin sensitivity. ER Ca2+ levels in islets from βS2KO mice were significantly reduced, while serum proinsulin/insulin (PI/I) ratios and whole pancreas PI/I content were elevated. Immunoblot analysis of βS2KO islets and S2KO INS-1 cells revealed reduced active forms of the proinsulin processing enzymes, PC1/3, PC2 and CPE. Restoration of SERCA2b via adenoviral transduction in S2KO INS1 cells was sufficient to restore PC1/3 and PC2 maturation and enzyme activity. Brefeldin A treatment in INS1 cells recapitulated the impairments in PC1/3 and PC2 maturation observed in S2KO cells, suggesting a disturbance in protein trafficking between the ER and Golgi. Consistent with this, trafficking assays were performed using a vesicular stomatitis virus G (VSVG) protein construct and revealed a significantly slower rate of VSVG movement from the ER to the Golgi in S2KO INS1 cells. Moreover, pancreas sections from βS2KO mice showed increased co-localization of proinsulin and ProPC2 in the early compartments of the secretory pathway. Taken together, these data suggest that loss of SERCA2 activity and ER Ca2+ loss in the pancreatic β cell leads to impaired proinsulin processing via reduced maturation and trafficking of proinsulin processing enzymes.
2023-10-11 | GSE207498 | GEO
Project description:Oryza sativa indica subgroup Assembly
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Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predominantly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress
Project description:Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced endoplasmic reticulum-mitochondria contacts (ERMCs) in therapy resistant cells, and genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance. ERMCs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ERMCs as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.
2021-11-18 | ST002054 | MetabolomicsWorkbench
Project description:ER+ve and ER-ve breast cancers tend to show different patterns of metastasis, with ER+ve tumours having a propensity to metastasize to the bone while ER-ve tumours tend to induce visceral metastasis. Glycans can play an important role in metastasis through their interactions with glycan binding proteins. Moreover we, and others have also shown that expression of particular tumor-associated glycoforms of the mucin MUC1, allows it to interact with lectins of the immune system. We now have data showing differences in the level of expression of some glycosyltransferases in ER+ve and ER-ve of breast cancer suggesting the expression of different O-linked glycoforms. RNA will be isolated from ER+ve and ER-ve primary breast cancers supplied by the Guy’s and St Thomas’ Research Breast Tissue Bank. Tumor tissue will be macro-dissected from thick cryostat sections by visual comparison with a representative H&E section. We will verify the level of expression of ER and document the expression of ST3Gal-I and ST6GalNAc-II by RT-qPCR. We have already isolated RNA from a number of tumours and shown we can obtain RNA of good quality with a RNA integrity number, as measured with an Agilent Bioanalyser, of >4.5 Since there is likely to be variability among primary tumors, ideally we analyzed of 10 ER negative and 9 ER positive tumours.
2011-09-25 | E-GEOD-32394 | biostudies-arrayexpress
Project description:Oryza sativa aromatic subgroup Genome sequencing and assembly
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Project description:Oryza sativa aus subgroup Genome sequencing and assembly
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