Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human prostatic cancer cell lines and sensitivity to an anticancer tumor agent

ABSTRACT: Transcriptional profiling was conducted on RNA from 16 prostatic cancer cell lines to identify genes whose expression level correlate with sensitivity of an anti-tumor agent Experiment Overall Design: Baseline gene expression profiling was performed using 16 prostatic cancer cell lines to identify expression signatures highly correlated with in vitro sensitivity to a particular agent

ORGANISM(S): Homo sapiens

SUBMITTER: Xi-De Wang

PROVIDER: E-GEOD-9633 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring.

Wang Xi-De XD Reeves Karen K Luo Feng R FR Xu Li-An LA Lee Francis F Clark Edwin E Huang Fei F

Genome biology 20070101 11

<h4>Background</h4>Dasatinib is a potent, multi-targeted kinase inhibitor that was recently approved for treatment of chronic myelogenous leukemia resistant to imatinib. To aid the clinical development of dasatinib in prostate cancer, we utilized preclinical models to identify potential molecular markers for patient stratification and efficacy monitoring.<h4>Results</h4>Using gene expression profiling, we first identified 174 genes whose expression was highly correlated with in vitro sensitivity ...[more]

PMID: 18047674

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Project description:Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen, a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified key pathways and regulators of prostatic differentiation including Wnt5a, BPM7, PTEN, and NKx3.1 using E-PZ-iPS-lke cells. Our results suggest that iPS-like cells can be derived from prostatic epithelial cells. These cells are pluripotent and capable of prostatic differentiation, and therefore provide a novel model for investigating epigenetic changes involved in prostate cell lineage specification.

Dataset Information

Transcription profiling of human prostatic cancer cell lines and sensitivity to an anticancer tumor agent

Publications

Identification of candidate predictive and surrogate molecular markers for dasatinib in prostate cancer: rationale for patient selection and efficacy monitoring.

Similar Datasets

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