Abstract 320: New metastatic murine prostate cancer cell lines and preclinical model of human prostate cancer.

Abstract

Abstract Defining oncogene-specific molecular pathways required for the induction and maintenance of prostate cancer is essential for the rational design of new therapies. Identifying molecular predictors of prostate cancer patient survival is important for patient therapeutic substratification. We generated murine prostate cancer cell lines via selective transduction with a single oncogene (c-Myc, Ha-Ras, NeuT, and v-Src). These cell lines demonstrate contact-independent growth characteristics in soft agar, and have the substantial growth advantage over primary prostate epithelial cells. Each of the prostate lines grew tumor in immune competent mice after subcutaneous injection, and develop lung metastasis in c-Myc, Ha-Ras, and v-Src cell line groups. RNA samples were prepared from the these cell lines, Microarray analysis identified a total of 2635 out of 22115 genes that were significantly altered in expression (at least two-fold change) in oncogene over-expressing cell lines when compared with prostate epithelial cell control samples. The distinct oncogene expression signature was compared to gene signatures obtained from other published databases to identify similarities to human prostate cancer phenotypes. Comparisons were performed against gene signatures representative of differential expression in advanced state vs. early stage prostate cancer, high grade vs low grade prostate cancer, recurrent vs. nonrecurrent, the results indicate a significant degree of similarity between the prostate oncogene expression signature and high-grade disease; between the oncogene expression signature and the advanced stage disease phenotype. Interrogation of two distinct cohorts of Prostate cancer patient samples using the oncogene signature demonstrated an ability to distinguish tumor from normal prostate with a predictive value for prostate cancer of 98 - 99%. The signature provided in blinded study independent substratification of reduced recurrence free survival by Kaplan-Meier analysis. The generation of new oncogene-specific prostate cancer cell lines that recapitulate human prostate cancer gene expression, that metastasize in immune-competent mice, are a valuable new resource for testing targeted therapy. The molecular signatures identified herein provide further value over current markers of prediction and outcome. Citation Format: Xiaoming Ju, Richard G. Pestell. New metastatic murine prostate cancer cell lines and preclinical model of human prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 320. doi:10.1158/1538-7445.AM2013-320