Somatic mutations activating MAPK signaling in disorders of brain overgrowth and in diffuse glioma have recently been reported in pediatric neurology. Here we developed a progressive zebrafish model of glioma based on somatic expression of oncogenes that activate MAPK-AKT signalling (H-RASG12V, K-RASG12D, AKT, EGFRv3, BRAFV600E) in neural progenitor cells. Oncogenic HRAS was the most effective in activating MAPK signaling and caused the development of different types of growth disorders in juvenile fish: from benign dysplasia/heterotopia to invasive tumors of the telencephalon, midbrain and cerebellum. We used this model to clarify the molecular events leading to malignant tumors instead of benign lesions. Specific signatures distinguish benign heterotopia from tumors and establish that tumors require persistent activation of MAPK/ERK. Moreover, analysis of global RNA expression showed that brain tumors expressed a gene signature similar to the mesenchymal glioblastoma subtype Overall design: We performed transcriptome analysis (RNA-Seq) of 3 UAS:HRASV12G brains, which carried tumorigenic lesions in the telencephalon, midbrain and IV ventricle and compared them with tumor free, age matched brains.
A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth.
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View SamplesSome cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. Here we show, using in vitro and in vivo prostate cancer models, that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR) dependent luminal epithelial cells to AR independent basal-like cells. This lineage plasticity is enabled by loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2 and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching. Overall design: LNCaP/AR prostate cell line was transduced with shNT or shTP53:RB1 hairpins and then RNA was harvested from these cell lines for gene epxression analysis.
SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer.
Cell line, Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling of exosomal RNA isolated from breast cancer patients before, during and after radiation therapy.
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA isolated from stroma cell (MRC5) or stroma/breast cancer cell co-culture (MRC5 and 1833).
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Cell line, Subject
View SamplesHT induces an OXPHOS metabolic editing of ER+ breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133hi/ERlo cells mediating metastatic progression, which is sensitive to dual targeted therapy
Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesPURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesPURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer.
A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
Specimen part, Disease stage
View SamplesPhosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sex, Specimen part, Time
View SamplesBone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).
NF-κB1 inhibits TLR-induced IFN-β production in macrophages through TPL-2-dependent ERK activation.
Specimen part
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