Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343040 | ENA |
REPOSITORIES: ENA
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Project description:Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting lineage plasticity facilitates therapeutic resistance. Mechanisms underlying prostate cancer lineage plasticity are unknown, and relevant experimental models are needed. We demonstrate Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation in the mouse. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates mouse tumors are comparable to human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors like Ezh2 and Sox2. Clinically relevant Ezh2 inhibitors restore androgen receptor expression and sensitivity to antiandrogen therapy. These findings uncover genetic mutations enabling prostate cancer progression, identify mouse models for studying prostate cancer lineage plasticity, and suggest an epigenetic approach for extending clinical responses to antiandrogen therapy.
2017-02-24 | GSE90891 | GEO
Project description:Molecular Basis of Neuroendocrine Prostate Cancer
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Project description:Prostate adenocarcinoma (AdPC) cells can undergo lineage switching to neuroendocrine cells and develop into therapy-resistant neuroendocrine prostate cancer (NEPC). While genomic/epigenetic alterations are shown to induce neuroendocrine differentiation via an intermediate stem-like state, RNA splicing factor SRRM4 can transform AdPC cells into NEPC xenografts through a direct neuroendocrine transdifferentiation mechanism. Whether SRRM4 can also regulate a stem-cell gene network for NEPC development remains unclear. Here, we use the Ion AmpliSeqTM Transcriptome Human Gene Expression Kit (AmpliSeq) to analyze the transcriptome of human AdPC cell line DU145 overexpressing SRRM4 via lentiviral transduction compared to the control, empty vector-transduced DU145 cells. This study reveals that SRRM4 induces a pluripotency gene network consisting of the stem-cell differentiation gene, SOX2. In summary, we report a novel mechanism by which SRRM4 drives NEPC progression via a pluripotency gene network.
2018-08-14 | GSE118104 | GEO
Project description:PAX5 promotes progression of neuroendocrine prostate cancer
| PRJNA533095 | ENA
Project description:Neuroendocrine prostate cancer (NEPC) is the most virulent subtype. Currently, there is an urgent need to identify new biomarkers and therapeutic targets in NEPC. The splicing factor SRRM4 was previously demonstrated to be highly expressed in NEPC, to promote expression of genes linked to neuroendocrine differentiation and cancer progression, and to promote alternate splicing of genes, including REST. One of REST’s binding protein is lysine specific demethylase 1 (LSD1). Importantly, a transcript variant of LSD1 called LSD1+8a is expressed in neuronal tissues and promotes neuronal gene expression. However, there was no information about LSD1+8a’s importance in prostate cancer. Using adenocarcinoma and NEPC patient-derived xenografts and clinical specimens, we determined that LSD1+8a was expressed exclusively in NEPC. Furthermore, LSD1+8a expression was significantly correlated with elevated mRNA expression of SRRM4. Using SRRM4-overexpressing prostate cancer cell lines, we determined that alternative splicing of LSD1+8a is directly mediated by SRRM4 and that LSD1+8a and SRRM4 co-regulate a unique program of cancer-promoting genes that is not regulated by canonical LSD1. Our findings demonstrate that measurement of LSD1+8a expression is a promising NEPC biomarker and suggest that targeting LSD1+8a in NEPC may be a useful strategy to block expression of genes linked to cancer progression.
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Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Profiling of prostate tissues in prostate cancer progression
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Project description:The DNA isolated from 44 either frozen or FFPE Neuroendocrine Neoplasm (NEN) was analysed by NGS, to identify genes more likely to be subject to sequence variations among 523 cancer-related ones.
2022-06-30 | E-MTAB-11529 | biostudies-arrayexpress