BRCA-deficient mouse mammary tumor organoids
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ABSTRACT:
PROVIDER: PRJEB22990 | ENA |
REPOSITORIES: ENA
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Project description:We report the gene expression profile in BRCA deficient tumors after treatment with saline, nanoparticle-formulated Talazoparib and free Talazoparib
2020-04-10 | GSE125206 | GEO
Project description:Mammary organoids harvested from ErbB3 DOX-KO mice, which utilize MMTV-Cre transgene expression in the LE to cause genomic recombination at floxed ErbB3 alleles in ErbB3FL/FL were cultured in the presence or absence of doxycycline to induce ErbB3 loss. The gene expression shift following DOX-induced ErbB3 loss in the 3D organoids was examined by microarray. Gene expression patterns were interrogated in mammary organoids from ErbB3 inducible-knockout mice cultured in the presence of absence of doxycycline. Three biological replicates of the experiment were performed, resulting in a total of 6 samples (3 treatment, 3 control).
2012-01-04 | E-GEOD-32129 | biostudies-arrayexpress
Project description:Worldwide, breast cancer (BRCA) is the most common malignant tumor in women. Adriamycin (ADR) is considered one of the most effective agents for the treatment of BRCA, but its efficacy as a curative agent is compromised by intrinsic resistance and the acquisition of multidrug resistance characteristics during chemotherapy. The underlying mechanisms resulting in ADR resistance in BRCA remain poorly understood. Long non-coding RNA (lncRNA) are abnormally expressed in many cancers and are highly involved in its pathogenesis, including drug resistance. In order to systematically study the role of lncRNA in the resistance of BRCA cells to ADR, we used lncRNA expression microarray to establish gene expression profiles of ADR resistant cell lines and ADR sensitive cell lines.
2020-08-01 | GSE155478 | GEO
Project description:RNAseq of Brca1-deficient mouse mammary tumors
| PRJNA625044 | ENA
Project description:Purpose:Triple negative breast cancer (TNBC) commonly metastasizes to the brain and predicts poor prognosis with limited therapeutic options. TNBC frequently harbors BRCA mutations translating to platinum sensitivity; platinum response may be augmented by additional suppression of DNA repair mechanisms through poly(ADP-ribose)polymerase (PARP) inhibition. We evaluated brain penetrance and efficacy of Carboplatin +/- the PARP inhibitor ABT888, and investigated gene expression changes in murine intracranial (IC) TNBC models stratified by BRCA and molecular subtype status. Experimental design:Athymic mice were inoculated intra-cerebrally with BRCA-mutant: SUM149 (basal), MDA-MB-436 (claudin-low), or BRCA-wild-type: MDA-MB-468 (basal), MDA-MB-231BR (claudin-low) TNBC cells and treated with PBS control (IP, weekly), Carboplatin (50mg/kg/week, IP), ABT888 (25mg/kg/day, OG), or their combination. DNA-damage (?-H2AX) and apoptosis (cleaved-Caspase-3(cC3)) were assessed via IHC of IC tumors. Gene expression of BRCA-mutant IC tumors was measured. Results: Carboplatin+/-ABT888 significantly improved survival in BRCA-mutant IC models compared to control, but did not improve survival in BRCA-wild-type IC models. Carboplatin+ABT888 revealed a modest survival advantage versus Carboplatin in BRCA-mutant models. ABT888 yielded a marginal survival benefit in the MDA-MB-436 but not in the SUM149 model. BRCA-mutant SUM149 expression of ?-H2AX and cC3 proteins was elevated in all treatment groups compared to Control, while BRCA-wild-type MDA-MB-468 cC3 expression did not increase with treatment. Carboplatin treatment induced common gene expression changes in BRCA-mutant models.Conclusions: Carboplatin+/-ABT888 improves survival in BRCA-mutant IC TNBC models with corresponding DNA damage and gene expression changes. Combination therapy represents a promising treatment strategy for patients with TNBC brain metastases warranting further clinical investigation. reference x sample
2015-05-12 | E-GEOD-55399 | biostudies-arrayexpress
Project description:The effectiveness and underlying mechanisms of organoid transplantation therapy in liver ischemia-reperfusion injury (IRI) remain underexplored. We aimed to investigate the therapeutic potential and biological processes of human adult stem cells (hASCs)-derived hepatic organoids (hHOs) in treating liver IRI in an immune-deficient murine model.
2024-05-13 | PXD052240 | iProX
Project description:Mammary organoids treated with a 28 day menstrual cycle profile of estradiol and progesterone with or without TPA: Comparison of normal versus BRCA1 mut cells. Purpose: The goals of this study are to determine 1) the effects of a 28 day menstrual cycle profile of estradiol and progesterone, 2) the effects of TPA, and 3) the responses in normal versus BRCA1 carriers, in benign breast organoids using RNA-seq
2019-12-10 | GSE131640 | GEO
Project description:M6 cells expression a similar genetic signature as the parent tumor, C3(1)Tag tumor. The mammary tumors, and tumor cell line, are distinct from normal mammary epithelial tissue (FVB) BRCA/p53, cmyc, h2n, p53ERneg, p53ERpos, pymt and ras samples were not reported in this paper.
2011-09-01 | GSE25488 | GEO
Project description:Cancer-associated fibroblasts (CAFs) give rise to desmoplastic stroma, which supports tumor progression and metastasis, and comprises up to 90% of the tumor mass in pancreatic cancer. Recent work by us and others has shown that CAFs are transcriptionally rewired by adjacent cancer cells to form heterogeneous subtypes. Whether this rewiring is differentially affected by different driver mutations in cancer cells is largely unknown. Here we address this question by dissecting and comparing the stromal landscape of BRCA-mutated and BRCA Wild-type (WT) pancreatic ductal adenocarcinoma (PDAC). We comprehensively analyze PDAC samples from a cohort of 42 patients by laser-capture microdissection, RNA-sequencing and multiplexed immunofluorescence, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA-WT tumors. In particular, we detect an increase in a subset of Clusterin (CLU)-positive CAFs in BRCA-mutated tumors. Using cancer organoids, co-cultures and in-vivo models we show that loss of BRCA function in cancer cells leads to a transcriptional shift of pancreatic stellate cells from myofibroblastic into immune-regulatory CLU+ CAFs. This process is mediated through activation of heat-shock factor 1 (HSF1), the transcriptional regulator of Clu. Our findings unravel a new dimension of stromal heterogeneity, influenced by germline mutations in cancer cells, with direct translational implications for clinical research.
2022-10-10 | GSE200616 | GEO
Project description:Cancer-associated fibroblasts (CAFs) give rise to desmoplastic stroma, which supports tumor progression and metastasis, and comprises up to 90% of the tumor mass in pancreatic cancer. Recent work by us and others has shown that CAFs are transcriptionally rewired by adjacent cancer cells to form heterogeneous subtypes. Whether this rewiring is differentially affected by different driver mutations in cancer cells is largely unknown. Here we address this question by dissecting and comparing the stromal landscape of BRCA-mutated and BRCA Wild-type (WT) pancreatic ductal adenocarcinoma (PDAC). We comprehensively analyze PDAC samples from a cohort of 42 patients by laser-capture microdissection, RNA-sequencing and multiplexed immunofluorescence, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA-WT tumors. In particular, we detect an increase in a subset of Clusterin (CLU)-positive CAFs in BRCA-mutated tumors. Using cancer organoids, co-cultures and in-vivo models we show that loss of BRCA function in cancer cells leads to a transcriptional shift of pancreatic stellate cells from myofibroblastic into immune-regulatory CLU+ CAFs. This process is mediated through activation of heat-shock factor 1 (HSF1), the transcriptional regulator of Clu. Our findings unravel a new dimension of stromal heterogeneity, influenced by germline mutations in cancer cells, with direct translational implications for clinical research.
2022-10-10 | GSE200615 | GEO