Abstract 4607: Androgen signaling is essential for prostate cancer development initiated from prostatic basal cells

Abstract

Abstract Emerging evidence has shown that both prostatic basal and luminal cells are able to initiate oncogenic transformation. However, despite the diversity of tumor initiating cells, most prostate cancer cells express the androgen receptor (AR) and depend on androgens for their growth and expansion, implicating an essential role of androgen signaling in prostate tumorigenesis. Prostatic basal cells express p63 and are able to differentiate into luminal, neuroendocrine, and basal cells. In this study, we used a variety of relevant mouse models and in vivo systems to directly address the significance of androgen signaling in oncogenic transformation and tumor development initiated from prostatic p63-expressing cells. We demonstrate that activating Wnt oncogenic signaling by expressing stabilized b-catenin in prostatic p63-expressing cells is able to induce cell proliferation and the formation of atypical cell clusters in different prostatic lobes at embryonic, prepubescent, and adult stages. Intriguingly, despite the androgen insensitive nature of prostatic p63-expressing cells, androgens are still essential for these cells to grow and develop to androgen-dependent, luminal cell type prostate tumors. These findings are consistent with what have been observed in human prostate cancers, in which the majority of tumor cells are androgen-sensitive and possess luminal cell properties, providing new insight into the molecular mechanisms for prostate cancer initiation and progression. Citation Format: Yongfeng He, Erika Hooker, Eun-Jeong Yu, Gerald R. Cunha, Lan Liao, Jianming Xu, Andrew Earl, Huiqing Wu, Michael L. Gonzalgo, Zijie Sun. Androgen signaling is essential for prostate cancer development initiated from prostatic basal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4607.