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

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. Overall design: 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.