Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Identifying actionable targets through integrative analyses of GEM model and human prostate cancer profiling [Agilent]

ABSTRACT: Here we prolife prostate cancers derived from GEM models of prostate cancer representative of human prostate cancer Total DNA was isolated from established prostate cancers in 4 GEM models of prostate cancer - PB-MYC, Pten-/-, Pten-/- p53-/-, Pten-/- Rosa26-ERG, and 3 cell lines derived from GEM models including CaP8, MYC CaP, and MPC3 and normalized to wild-type prostate of litter-mate mice of same genetic background strain

ORGANISM(S): Mus musculus

SUBMITTER: Jeffrey Zhao

PROVIDER: E-GEOD-61382 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identifying actionable targets through integrative analyses of GEM model and human prostate cancer genomic profiling.

Wanjala Jackie J Taylor Barry S BS Chapinski Caren C Hieronymus Haley H Wongvipat John J Chen Yu Y Nanjangud Gouri J GJ Schultz Nikolaus N Xie Yingqiu Y Liu Shenji S Lu Wenfu W Yang Qing Q Sander Chris C Chen Zhenbang Z Sawyers Charles L CL Carver Brett S BS

Molecular cancer therapeutics 20141107 1

Copy-number alterations (CNA) are among the most common molecular events in human prostate cancer genomes and are associated with worse prognosis. Identification of the oncogenic drivers within these CNAs is challenging due to the broad nature of these genomic gains or losses which can include large numbers of genes within a given region. Here, we profiled the genomes of four genetically engineered mouse prostate cancer models that reflect oncogenic events common in human prostate tumors, with t ...[more]

PMID: 25381262

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Project description:Key histological and growth progression characteristics of human prostate cancer are phenocopied in mouse models that have been subjected to androgen level depletion and engineered for hemizygosity of candidate prostate cancer tumor suppressor genes Nkx3.1 and Pten. To characterize their relative transcriptomes and identify a genomic basis for their relevance to human prostate cancers, we compared mouse prostate tumors expression profiles to those from a panel of human prostate cancer isolates and to normal and benign prostates. Human prostate cancers and mouse prostate tumor models both exhibit the activation of genes associated with growth, cell cycle control, and inhibition of differentiation (CDKN2A, CDKN2B, CDKN2C, CEBPB, CEBPG, CSF1, CTSS, DMBT1, EGFR, PLCG2, PXN, SPP1, TNFSF9), and conversely, diminished expression of genes associated with normal prostate differentiation and function. All tumors also exhibit dysregulated expression of genes associated with inflammation, the disruption of prostate-associated ER stress pathways, as well as with oxidative stress, energy metabolism, cell adhesion, and stress response. Immunoinflammatory and altered cell adhesion process-associated genes exhibited prominent expression in early stage tumors. In contrast, metastatic human prostate cancer samples eliminated the expression of most immunoinflammatory-associated transcripts. Cross-species comparisons of molecular programs that are shared or distinguishing of Nkx3.1; Pten mutant mouse models and human adenocarcinomas clearly delineate core tumorigenesis programs associated with cell cycle activation and loss of differentiation. Compared to locally spreading mouse and human tumors, metastatic prostate cancer exhibits greatly reduced expression of immunoinflammatory and adhesion genes, implying that immuno-inflammatory activation may enable first stages of tumorogenesis, but suppress metastasis. These results provide a novel framework to identify stage-specific biomarkers and candidate targets for combinatorial therapeutics. The complex role of inflammation suggests a need for additional caution in countering metastasis. Keywords: tumor stage 26 Affymetrix MOE430A microarrays

Dataset Information

Identifying actionable targets through integrative analyses of GEM model and human prostate cancer profiling [Agilent]

Publications

Identifying actionable targets through integrative analyses of GEM model and human prostate cancer genomic profiling.

Similar Datasets

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