Project description:This SuperSeries is composed of the following subset Series: GSE25461: Gene expression of three prostate lobes, ventral prostate (VP), dorsal lateral prostate (DLP), and anterior prostate (AP), by cholesterol diet GSE25472: Gene expression of LNCaP human prostate cells by cholesterol diet Refer to individual Series
Project description:Understanding the systemic regulation of normal prostate gene expression by cholesterol diet is critical for deciphering the mechanisms responsible for the transition from healthy to pathogenic prostate conditions. To understand mechanism under cholesterol effect on prostate, we performed microarray analysis using prostate tissues from SCID or C57BL/6 mice feed with varying diet conditions containing high, low or normal cholesterol. The RNA is obtained from ventral prostate (VP), dorsal lateral prostate (DLP), and anterior prostate (AP) in 18 SCID mice.
Project description:PB-Cre/Pten/Smad4 is a transgenic mouse model of metastatic prostate adenocarcinoma (PMID: 21289624). To study the transcriptomic alterations associated with castration-resistant prostate cancer (CRPC), the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. After about 4 weeks, dorsolateral prostate (DLP) lobes of treatment-naïve prostate tumors (N=2) and CRPC tumors (N=3) were harvested and extracted for RNA purification and microarray profiling. To further study the transcriptomic changes associated with lung metastases of the PB-Cre/Pten/Smad4/mTmG CRPC model, the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. About 3 months later, from one mouse anterior prostate (AP), dorsolateral prostate (DLP), ventral prostate (VP) and GFP+ lung metastasis nodules were each harvested for RNA purification and microarray profiling.
Project description:High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression. C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR. Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. GPx3 mRNA levels were decreased by approximately 2-fold by high fat diet in all 3 prostate lobes. In human non-transformed prostate cells (PrSC, PrEC and BPH-1), cholesterol loading decreased GPx3 expression, and increased H2O2 levels of culture medium. Troglitazone increased GPx3 expression in 3 normal prostate cells, and decreased H2O2 levels. In addition, troglitazone attenuated cholesterol-induced H2O2 increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score. High fat diet alters pathways related to many genes concerned with oxidative stress. GPx3, a gene identified by this analysis, was found to be down regulated by high fat diet and appears be decreased in human prostate cancers, suggesting that GPx3 may have a possible role in modulating carcinogenesis.
Project description:Cancer of the prostate is influenced both by genetic predisposition and environmental factors. The identification of genes capable of modulating cancer development has the potential to unravel disease heterogeneity and aid diagnostic and prevention strategies through improved understanding of gene-environment interactions. To this end, mouse models have been developed to isolate the influences of individual genetic lesions in the context of consistent genotypes and environmental exposures. However, the extent of normal prostatic phenotypic variability dictated by a genetic background potentially capable of influencing the process of carcinogenesis has not been established. In this study we used microarray analysis to quantitate transcript abundance levels in the prostates of five commonly studied inbred mouse strains. We applied a multiclass response t-test to identify genes whose expression in each strain significantly differed from the other four strains. Approximately 13% (932 genes) exhibited significant differential expression (range 1.3 to 190-fold) in one strain relative to other strains (FDRM-bM-^IM-$10%). The pattern of variability in transcript levels did not result from variations unique to a particular strain, but rather represented genetic variability across all five strains assessed. Expression differences were confirmed by qRT-PCR, or immunohistochemistry for several genes previously shown to influence cancer progression such as Psca, Mmp7, and Clusterin. Analyses of human prostate transcripts orthologous to variable murine prostate genes identified differences in gene expression in benign epithelium that correlated with the differentiation state of adjacent tumors. For example, the expression of apolipoprotein D, a gene known to enhance resistance to cell stress in Drosophila, was expressed at significantly greater levels in benign epithelium associated with high-grade versus low-grade cancers. These data support the concept that the cellular, tissue, and organismal context contribute to oncogenesis and suggest that a predisposition to a sequence of events leading to pathology may be determined prior to cancer initiation. Prostates from twelve mice from each of five strains of Mus musculus: C57BL/6J, 129X1/SvJ, BALB/cAnCrl, FVB/NJ and DBA/2NCrl, were resected and individual lobes were dissected: DP: dorsal prostate; LP: lateral prostate; VP: ventral prostate; AP: anterior prostate. Each experimental sample represents a pool of equal amounts of RNA for each prostatic lobe from 3 animals. Four independent experimental samples were created per strain: 12 mice divided into 4 pools of 3 mice each for a total of 4 microarray experiments per strain. Amplified RNA from each experimental sample was hybridized against a reference sample (created by combining equal amounts of RNA from all the samples from all strains) onto custom mouse prostate cDNA microarrays using alternate dye-labeling to account for dye-specific effects.
Project description:High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression. C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR. Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. GPx3 mRNA levels were decreased by approximately 2-fold by high fat diet in all 3 prostate lobes. In human non-transformed prostate cells (PrSC, PrEC and BPH-1), cholesterol loading decreased GPx3 expression, and increased H2O2 levels of culture medium. Troglitazone increased GPx3 expression in 3 normal prostate cells, and decreased H2O2 levels. In addition, troglitazone attenuated cholesterol-induced H2O2 increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score. High fat diet alters pathways related to many genes concerned with oxidative stress. GPx3, a gene identified by this analysis, was found to be down regulated by high fat diet and appears be decreased in human prostate cancers, suggesting that GPx3 may have a possible role in modulating carcinogenesis. Control group:5 C57BL/6J mice (Taconic, Hudson, NY), 8-weeks of age, fed control diet ad libitum for 12 weeks; Experimental group: 5 C57BL/6J mice (Taconic, Hudson, NY), 8-weeks of age, fed ad libitum high fat diet for 12 weeks.
Project description:We reported the gene expression profiles of prostate dorsal-lateral-ventral glands of prostate-specific Pten-/- mice on AIN93M diet, 60%Kcal high-fat diet, and AIN93M diet containing 0.05% delta-tocotrienol at 20 weeks of age.
Project description:MED1 is a transcriptional coactivator for gene-specific activators involved in growth and development, we were interested in identifying MED1 target genes potentially involved in prostate development by cDNA microarray. Med1 was conditional knocked out in mice prostate. We performed cDNA microarray with two sets: (1) RNA isolated from three WT ventral prostates and three MT ventral prostates; (2) RNA isolated from three WT lateral prostates and three MT lateral prostates. We used microarrays to detail the global programme of gene expression underlying how Med1 was involved in mice prostate development by regulating targeted genes expression 12 mice prostate samples were divided into two groups: (1) three WT ventral prostates and three MT ventral prostates; (2) three WT lateral prostates and three MT lateral prostates.
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.
Project description:MED1 is a transcriptional coactivator for gene-specific activators involved in growth and development, we were interested in identifying MED1 target genes potentially involved in prostate development by cDNA microarray. Med1 was conditional knocked out in mice prostate. We performed cDNA microarray with two sets: (1) RNA isolated from three WT ventral prostates and three MT ventral prostates; (2) RNA isolated from three WT lateral prostates and three MT lateral prostates. We used microarrays to detail the global programme of gene expression underlying how Med1 was involved in mice prostate development by regulating targeted genes expression