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
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
Project description:Gene expression profiling of TRAMP-C2, transgenic adenocarcinoma of mouse prostate, cell line. The experiment was done to see which genes were over- or underexpressed in the cell line. The results were combined with aCGH results of the same samples (experiment Gene copy number profiling of TRAMP-C2 cell line using aCGH) to see, whether the copy number status had any effect on gene expression.
Project description:Osteopontin (OPN) is a secreted glycoprotein, belonging to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer cells has been associated with disease progression, androgen independence and metastases. Nevertheless the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a spherical homogeneous tumor in about 60% of OPN-/- TRAMP mice that seldom occurs in parental TRAMP mice. Histology and immunohistochemistry characterized these tumors for being Tag positive but negative for AR, highly proliferative and endowed of neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus -sufficient TRAMP tumors. Down-regulated genes included key genes of TGFï?¢ pathway, and a role for TGFï?¢ in NE differentiation of prostate cancer was also confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human NE tumours. These data underscore a novel role of OPN at early stages of prostate cancer growth, protecting against the development of aggressive NE tumors. Total RNA obtained from prostate tumors from 18 and 30 weeks old TRAMP mice, compared to RNA extracted from prostate tumors and prostate tissue from Osteopontin-deleted TRAMP mice
Project description:Gene expression profiling of TRAMP-C2, transgenic adenocarcinoma of mouse prostate, cell line was done after treating the cells with DNA demethylating agent 5-aza-2'-deoxycytidine (5azadC; Sigma-Aldrich, St. Louis, MO) and histone deacetylase inhibitor trichostatin A (TSA; Sigma-Aldrich), both separately and in combination. These treatments relieve epigenetic modifications, and thus reveal potentially epigenetically silenced genes amongst the genes with increased expression after the treatments.
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
Project description:Tumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis. Using the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and a fold change comparison system we identified genes that are associated with immune tolerance to be up-regulated and genes associated with immunity to be down regulated in tumor associated dendritic cells. Keywords: Comparative gene expression, prostate cancer, dendritic cells
Project description:There is an urgent need for new biomarkers to enhance the clinical management of prostate cancer. Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to test the utility of a mouse model of prostate cancer as a tool to discover serum miRNAs that could be applied in a clinical setting. Global miRNA profiling using microarrays identified 46 miRNAs at differential levels in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice compared to their wild-type littermates. Total RNA extracted from the serum of 9 mice with advanced disease was pooled into 3 groups (TRAMP serum RNA 1, 2 and 3). Serum RNA from age-matched wild-type littermates, pooled as above, served as the control set.
Project description:The mechanism of action of vitamin D in prostate cancer (PCa) remains poorly defined, with most mechanisms identified being highly cell type and model specific. One of the underlying factors for these diverse mechanisms may be the use of overly simplistic in vitro model systems to study the complex biology of vitamin D response. Here we use the more complex and in vivo transgenic adenocarcinoma of mouse prostate (TRAMP) model to better determine the mechanism by which vitamin D inhibits PCa growth. In these studies early stage TRAMP mice were treated ± 20μg/kg calcitriol (vitamin D) on a Monday/Wednesday/Friday schedule and tissue was procured 12 and 24 hours post treatment to assess changes in PCa transcriptomes using Affymetrix gene expression arrays.
Project description:The mechanism of action of vitamin D in prostate cancer (PCa) remains poorly defined, with most mechanisms identified being highly cell type and model specific. One of the underlying factors for these diverse mechanisms may be the use of overly simplistic in vitro model systems to study the complex biology of vitamin D response. Here we use the more complex and in vivo transgenic adenocarcinoma of mouse prostate (TRAMP) model to better determine the mechanism by which vitamin D inhibits PCa growth. In these studies early stage TRAMP mice were treated M-BM-1 20M-NM-<g/kg calcitriol (vitamin D) on a Monday/Wednesday/Friday schedule and tissue was procured 12 and 24 hours post treatment to assess changes in PCa transcriptomes using Affymetrix gene expression arrays. 15 total samples were analyzed. 10 week old TRAMP mice were treated IP M-BM-1 20 ug/kg calcitriol on a Monday/Wednesday/Friday (MWF) schedule, and prostate tissue was procured 12 (N=3, control; N=4, calcitriol) and 24 hours (N=4, control; N=4, calcitriol) post treatment for use in affymetrix studies.