Abstract 1201: Establishment and characterization of cell lines derived from a murine model of PTEN-deficient prostate cancer

Abstract

Abstract Inactivation of the tumor suppressor PTEN is a common event in human prostate cancer that leads to increased activation of the PI3K pathway. Crosstalk between the PI3K signaling cascade and other cancer regulatory pathways contributes to the growth and survival of cancer cells. To better understand the mechanisms involved in the transformation process and to establish an in vivo screening system for novel treatment strategies, we previously developed a genetically engineered mouse model of prostate cancer that is based on the conditional inactivation of PTEN. In this model, inactivation of PTEN results in the stage-specific development of prostate cancer that recapitulates most features of the human disease including the development of castration-resistant prostate cancer (CRPC). The purpose of our study was to establish and characterize a panel of cell lines derived from this model in order to study the disease mechanisms at the cellular level and to establish a cell-based assay system to complement our in vivo program for pre-clinical screening of novel anticancer drugs. A panel of 7 cell lines derived from castration-naïve prostate tumors and 6 cell lines derived from CRPC were established. Cells lines were characterized for morphological, growth, differentiation, and molecular profiles in vitro as well as for their tumorigenic potential in vivo. The cell lines were also tested against a panel of cytotoxic and molecular targeting drugs and compared to the sensitivity of human prostate cell lines. Overall, our comprehensive analysis summarizes the functionality and potential application as cell-based system for developing treatment strategies against prostate cancer. Citation Format: Kazuhiro Yoshikawa, Marco A. De Velasco, Yurie Kura, Naomi Ando, Emiko Fukushima, Yuji Hatanaka, Yutaka Yamamoto, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuto Nishio, Hirotsugu Uemura. Establishment and characterization of cell lines derived from a murine model of PTEN-deficient prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1201. doi:10.1158/1538-7445.AM2014-1201