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Candidate Gene Identification Through RNA-Seq Analysis of (TRAMP x WSB/EiJ) F2 Primary Tumors

ABSTRACT: RNA-seq analysis of 115 randomly selected (TRAMP x WSB/EiJ) F2 prostates that had been harvested at experimental termination was performed to identify metastasis associated transcriptomic changes

ORGANISM(S): Mus musculus

PROVIDER: GSE108131 | GEO | 2018/05/14

REPOSITORIES: GEO

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Candidate Gene Identification Through RNA-Seq Analysis of (TRAMP x WSB/EiJ) F2 Primary Tumors

Project description:Candidate Gene Identification Through RNA-Seq Analysis of (TRAMP x WSB/EiJ) F2 Primary Tumors

| PRJNA422530 | ENA

Testis expression in Mus musculus domesticus WSB/EiJ x Mus musculus musculus PWD/PhJ F2 hybrids

Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven M-bM-^@M-^Xhotspots,M-bM-^@M-^Y seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a M-bM-^@M-^XfertileM-bM-^@M-^Y subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.

2014-05-01 | E-GEOD-54089 | biostudies-arrayexpress

Candidate Gene Identification Through RNA-Seq Analysis of (TRAMP x J:DO) F1 Primary Tumors

Project description:RNA-seq analysis of 195 randomly selected (TRAMP x J:DO) F1 prostates that had been harvested at experimental termination (210 days or humane endpoints) was performed to identify metastasis associated transcriptomic changes

2017-01-01 | GSE89207 | GEO

Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP)

Project description:Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy In this study, we have generated an open source TRAMP microarray dataset to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 9 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes). Keywords: prostate cancer, TRAMP

2008-12-31 | GSE10525 | GEO

Transcription profiling of mouse transgenic adenocarcinoma of the prostate (TRAMP)

Project description:Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy; In this study, we have generated an open source TRAMP microarray dataset to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 9 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes). Experiment Overall Design: normal prostate vs. TRAMP

2009-01-14 | E-GEOD-10525 | biostudies-arrayexpress

Gene expression analysis of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.

Project description:Analysis of gene expression of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.The hypothesis tested in the present study was that mast cells inhibition or absence impacted prostate tumor development and histotype. Results demonstrate that prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated have a neuroendocrine signature. Total RNA obtained from prostate tumors from 24 wks old TRAMP mice chronically treated with sodium chromoglycate (cromolyn) since 8 wks of age, and from 24 wks old TRAMP KitW-sh mice, compared to untreated 30 wks old TRAMP mice and to non tumoral prostates

2011-06-15 | E-GEOD-29956 | biostudies-arrayexpress

Expression data from the dorsal and lateral lobes of the prostates of TRAMP mice treated with OSU-CG5

Project description:Cells undergoing malignant transformation often shift their cellular metabolism from primarily oxidative phosphorylation to aerobic glycolysis (the Warburg effect). Energy restriction-mimetic agents (ERMAs), such as 2-deoxyglucose and resveratrol, that target this shift in cellular metabolism have been effective in inhibiting cancer cell growth in vitro, and xenograft tumor growth in vivo. We recently developed a novel ERMA, OSU-CG5, that exhibits higher in vivo activity than previously described ERMAs. In this study, we investigated the effect of OSU-CG5 on global gene expression in the dorsal and lateral lobes of the prostate of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, and on its ability to suppress lesion progression in these mice. Intact male TRAMP mice were randomized into 2 groups and treated for 4-weeks (from age 6 to 10 weeks) with a vehicle or 100 mg/kg/day OSU-CG5 via oral gavage. At the end of the study, the urogenital tracts were collected and prostates microdissected. RNA was extracted from the dorsal and lateral lobes of the prostates from 3 mice per group, and Affymetrix microarrays were performed.

2013-01-06 | E-GEOD-32422 | biostudies-arrayexpress

HDX-MS of the TRAMP Complex with tRNA

Project description:TRAMP is a eukaryotic protein complex with RNA helicase and polyadenylase activity that marks and delivers a variety of RNA substrates to the nuclear exosome for degradation. Prior work has characterized binding of Trf4 and Air2 to the helicase core of Mtr4 and the regulation of both enzymatic activities in TRAMP. Air2 contains a conserved sequence that is predicted to bind the arch domain of Mtr4, though this interface is dispensable for TRAMP formation. To understand the interactions of the Saccharomyces cerevisiae TRAMP complex and its interactions with RNA, we have applied hydrogen-deuterium exchange mass spectrometry. We demonstrate that Air2 simultaneously binds the helicase core and the fist of Mtr4 in solution, constraining the arch to a conformation ready to bind RNA. We characterize the previously unknown interactions of Trf4 and Air2 with RNA and show how interactions with substrates are altered in TRAMP, supporting a mechanistic model for the enhancement of Mtr4 activity in TRAMP.

2024-12-11 | PXD053773 | Pride

Expression data derived from adenocarcinoma or neuroendocrine prostate cancer of TRAMP and SPARC deficient TRAMP mice.

Project description:In this dataset we show transcriptional profiles derived from adenocarcinoma or incipient neuroendocrine prostate cancer (NEPC) derived from TRAMP or SPARC-deficient TRAMP mice respectively. Genetic ablation of SPARC rendered prostate cancer cells to be prone to NEPC differentiation.

2024-07-01 | GSE242811 | GEO

Substrate Specificity of the TRAMP Nuclear Surveillance Complexes

Project description:During nuclear surveillance in yeast, the RNA exosome functions together with the TRAMP complexes. These include the DEAH-box RNA helicase Mtr4 together with an RNA-binding protein (Air1 or Air2) and a poly(A) polymerase (Trf4 or Trf5). To better determine how RNA substrates are targeted, we analyzed protein and RNA interactions for TRAMP components. Mass spectrometry identified three distinct TRAMP complexes formed in vivo. These complexes preferentially assemble on different classes of transcripts. Unexpectedly, on many substrates, including pre-rRNAs and pre-mRNAs, binding specificity was apparently conferred by Trf4 and Trf5. Clustering of mRNAs by TRAMP association showed coenrichment for mRNAs with functionally related products, supporting the significance of surveillance in regulating gene expression. We compared binding sites of TRAMP components with multiple nuclear RNA binding proteins, revealing preferential colocalization of subsets of factors. TRF5 deletion reduced Mtr4 recruitment and increased RNA abundance for mRNAs specifically showing high Trf5 binding.

2020-07-02 | PXD017114 | Pride

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