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Primary mouse prostate organoid culture with overexpression of FOXA1

ABSTRACT: Primary mouse prostate organoid culture with overexpression of FOXA1

PROVIDER: PRJNA528458 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8741790_1.fastq.gz	Fastqsanger.gz
	SRR8741790_2.fastq.gz	Fastqsanger.gz
	SRR8741800_1.fastq.gz	Fastqsanger.gz
	SRR8741800_2.fastq.gz	Fastqsanger.gz
	SRR8741810_1.fastq.gz	Fastqsanger.gz

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Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1

Project description:Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1

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Chromatin Landscape Analysis of primary mouse prostate organoid culture with overexpression of FOXA1

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Genomic analyses of primary mouse prostate organoid culture with overexpression of FOXA1

Project description:Mutations in the FOXA1 transcription factor define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown. By annotating the FOXA1 mutation landscape from 3086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (~50% of all mutations) and R219 (~5%), a highly conserved DNA contact residue. Clinically, Wing2 mutations are seen in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumors with neuroendocrine histology. Interrogation of the biologic properties of FOXA1WT and 14 FOXA1 mutants revealed gain-of-function in mouse prostate organoid proliferation assays. ATAC-seq of FOXA1WT and representative Wing2 and R219 mutants revealed dramatic, mutant-specific changes in open chromatin at thousands of genomic loci, together with novel sites of FOXA1 binding and associated increases in gene expression. Of note, peaks in R219 mutant expressing cells lack the canonical core FOXA1 binding motifs (GTAAAC/T) but are enriched for a related motif (GTAAAG/A), which is preferentially activated by R219 mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its normal pioneering function and promote oncogenesis through perturbation of normal luminal epithelial differentiation programs, providing further support to the role of lineage plasticity in cancer progression.

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Genomic analyses of primary mouse prostate organoid culture with overexpression of FOXA1

Project description:Genomic analyses of primary mouse prostate organoid culture with overexpression of FOXA1

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Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1

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Effect of FOXA1 overexpression in prostate cancer

Project description:FOXA1 is a transcription factor which aids AR function in prostate. There is controversary over the effect of high FOXA1 level has on prostate cancer so we forced the overexpression in the LNCaP prostate cancer cell line. LNCaP prostate cancer cell line was transfected with GFP control plasmid or plasmid containing FOXA1 full length cDNA. The effect on gene expression was assessed by microarray.

2014-01-03 | E-GEOD-49153 | biostudies-arrayexpress

Effect of FOXA1 overexpression in prostate cancer

2014-01-03 | GSE49153 | GEO

Primary prostate organoid transcriptomic profile in co-culture with primary prostate stroma

Project description:Organotypic in vitro culture is useful to model mammalian disease in numerous tissues. Normal epithelial differentiation and carcinogenesis both undergo in vivo regulation by stroma, but current culture methods exclude stroma. To mimic this in vivo environment, we developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells supported increased organoid formation and expressed growth factors and WNT-related genes involved in epithelial differentiation. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Tumoroids derived from primary prostate cancer maintained differential expression of the prostate cancer marker AMACR only in the presence of stroma. Stroma-induced phenotypes were similar in all patients examined, yet maintained inter-patient heterogeneity in the degree of response. Addition of stroma to in vitro organoid culture recapitulated the in vivo microenvironment by inducing organization of benign organoids into branching structures and preserving prostate cancer phenotypes.

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Project description:FoxA1 has been shown critical for prostate development and prostate-specific gene expression regulation. In addition to its well-established role as an AR pioneering factor,several studies have recently revealed significant AR binding events in prostate cancer cells with FoxA1 knockdown. Furthermore, the role of FoxA1 itself in prostate cancer has not been carefully examined. Thus, it is important to understand the role of FoxA1 in prostate cancer and how it interacts with AR signaling. To address these questions, we generated engineered LNCaP cells with FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression. We performed microarray analysis of these cells. We performed microarray analysis on LNCaP cells with FoxA1 knockdown using shRNA or siRNA, 22RV1 cells with stable FoxA1 knockdown and PC3M cells with FoxA1 stable overexpression

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