Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects of minor salivary glands: parallels to glandular duct morphogenesis in prostate.
Collectively, our work highlights a novel hierarchical transcriptional regulatory network between NKX3-1, AR, and the RAB GTPase signaling pathway that is critical for the genetic-molecular-phenotypic paradigm in androgen-dependent prostate cancer.
The decrease of FOXA1 and NKX3-1, and aberrant activation of AR, thus accounts for the decrease of DRAIC during prostate cancer progression to the CR state.
Here, we provide an overview of the transcription factors that are important in normal prostate homeostasis (NKX3-1, p63, androgen receptor [AR]), primary prostate cancer (ETS family members, c-MYC), castration-resistant prostate cancer (AR, FOXA1), and AR-independent castration-resistant neuroendocrine prostate cancer (RB1, p53, N-MYC).