Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of AZD1208 on gene expression in recurrent resistant Myc-CaP tumors grown in castrated mice.


ABSTRACT: AZD1208 is a novel PIM kinase inhibitor that we have shown inhibits tumorigenesis in tissue recombination models, Myc-CaP allograft models, and human prostate cancer xenografts. We sought to determine the intracellular pathways that are responsible for the anti-tumor effect. To this end we used the tissue recombination protocol to implant MYCCaP cells into castrated mice. MYCCaP cells are an androgen-dependent mouse cell line that overexpresses the oncogene MYC. The mice used for implantation were castrated, so any tumors that result from the grafting procedure are androgen-independent. The grafted mice were divided into a control population receiving vehicle, and a test population receiving AZD1208. The tumors were harvested and in vitro cell lines were made. The new cell lines have been perpetuated in androgen-depleted media. RNA was harvested from three cell lines from mice receiving vehicle, three cell lines from mice receiving AZD1208, and from the parental MYCCaP cell line which was raised in media containing androgen. The RNA was hybridized to nine Affymetrix Mouse Gene 2.0 ST Arrays in the Vanderbilt University microarray processing core.

ORGANISM(S): Mus musculus

SUBMITTER: Philip Anderson 

PROVIDER: E-GEOD-59106 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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<h4>Background</h4>PIM1 kinase is coexpressed with c-MYC in human prostate cancers (PCs) and dramatically enhances c-MYC-induced tumorigenicity. Here we examine the effects of a novel oral PIM inhibitor, AZD1208, on prostate tumorigenesis and recurrence.<h4>Methods</h4>A mouse c-MYC/Pim1-transduced tissue recombination PC model, Myc-CaP allografts, and human PC xenografts were treated with AZD1208 (n = 5-11 per group). Androgen-sensitive and castrate-resistant prostate cancer (CRPC) models were  ...[more]

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