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

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

PROVIDER: PRJNA473572 | ENA |

REPOSITORIES: ENA

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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.

2018-05-30 | GSE115052 | GEO

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

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

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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

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Chromatin Landscape Analysis 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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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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Gene expression profiles of reactive stroma in prostate cancer

Project description:This is an analysis of stroma from 17 Grade 3 reactive stroma prostate cancer tissues and matched normal peripheral zone tissues. Keywords: two group comparison Laser capture microdissection and expression array analysis of stroma from 17 Grade 3 reactive stroma prostate cancer tissues and matched normal peripheral zone tissues.

2009-06-01 | E-GEOD-11682 | biostudies-arrayexpress

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