Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse prostate after castration and hormone replacement

ABSTRACT: In this study, we used microarray analysis to determine gene expression profile changes in the mouse prostate following castration and hormone replacement. We first identified genes with significant expression changes in each of these two processes and then generated a list of androgen responsive genes and a list of genes whose expression were inversely correlated with the presence of androgen. The analysis of this data set is described in Wang et al., Differentiation, 2006 Experiment Overall Design: C57/B6 mice of 10-12 weeks old (Charles River, Hollister, CA) were used. Mice were castrated, and at 3 or 14 days after surgery (C3 or C14), mice from these groups were sacrificed and whole prostates were collected. Prostates were also collected from sham-treated mice for control (N3). To obtain re-growing or regenerating prostate, mice that had been castrated 14 days before were implanted with testosterone (T) pellet (15 mg/pellet/mouse, Innovative Research, Sarasota, FL). Three days after pellet implantation, mice were sacrificed and prostates were collected (C14+T3). Five mice were used for each treatment/time point. Total RNA was purified with RNeasy kit.

ORGANISM(S): Mus musculus

SUBMITTER: Zemin Zhang

PROVIDER: E-GEOD-5901 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression profiling of the mouse prostate after castration and hormone replacement: implication of H-cadherin in prostate tumorigenesis.

Wang Xi-De XD Wang Bu-Er BE Soriano Robert R Zha Jiping J Zhang Zemin Z Modrusan Zora Z Cunha Gerald R GR Gao Wei-Qiang WQ

Differentiation; research in biological diversity 20061211 3

Mice have been used extensively for studying normal prostate development and for generation of transgenic or knock-out prostate cancer animal models. To understand systematically and thoroughly the androgen responsive program in the mouse prostate, we carried out microarray analysis to profile gene expression changes during prostate involution and re-growth triggered by castration and subsequent hormone replacement. Genes with significant changes in these two processes were identified and gene o ...[more]

PMID: 17288544

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Project description:Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen-deprivation remain poorly described despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild type mouse prostates a rare population of luminal progenitor cells that we called LSCmed according to their FACS profile (Lin?/Sca-1+/CD49fmed). Here we investigated the prevalence and castration resistance of LSCmed in various mouse models of prostate tumorigenesis. In intact mice, we show that LSCmed prevalence remains low (5-10% of epithelial cells) when prostatic androgen receptor signaling unaltered (malignant Hi-Myc mice) but significantly increases in models exhibiting reduced prostatic androgen receptor signaling, rising up to 30% in premalignant tumors (Pb-PRL mice) and to >80% in castration-resistant prostate tumors driven by Pten loss (Ptenpc-/- mice). LSCmed tolerance to androgen deprivation was demonstrated by their persistence (Ptenpc-/-) or further enrichment (Pb-PRL) 2-3 weeks after castration as evidenced by FACS analysis. Transcriptomic analysis revealed that LSCmed represent a unique cell entity as their gene-expression profile is different from luminal and basal/stem cells, but shares markers of each. Their intrinsic androgen signaling is markedly decreased, which explains why LSCmed tolerate androgen-deprivation. This also enlightens why Ptenpc-/- tumors are castration-resistant since LSCmed represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSCmed on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSCmed in various mouse prostate specimens. In castrated Ptenpc-/- prostates, BrdU staining revealed massive proliferation of CK4+ cells, further demonstrating their key role in castration-resistant prostate cancer progression. In all, this study identifies LSCmed as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate-resistant prostate cancer.

Dataset Information

Transcription profiling of mouse prostate after castration and hormone replacement

Publications

Expression profiling of the mouse prostate after castration and hormone replacement: implication of H-cadherin in prostate tumorigenesis.

Similar Datasets

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