Nuclear receptor profiling in prostatospheroids and castration-resistant prostate cancer.
Nuclear receptors (NRs), which belong to a superfamily of transcription factors and consist of a total of 48 members in humans, govern the expression of genes involved in a board range of developmental, reproductive, metabolic and immunological programs. Given the significant importance of androgen receptor and a few known NRs in the progression of prostate cancer, we surveyed the expression profiles of the entire NR superfamily in three-dimensional cultured prostatospheroids derived from different prostate cancer cell lines and a tumor xenograft model of castration-resistant prostate cancer VCaP-CRPC by quantitative real-time RT-PCR. Our results revealed that prostatospheroids and castration-relapse VCaP-CRPC xenografts, both contained enriched populations of prostate cancer stem/progenitor-like cells (PCSCs), displayed distinct expression patterns of NRs. Intriguingly, most of these differentially expressed NRs were orphan NRs and showed upregulation. Pairwise analysis identified five orphan NRs (including RORβ, TLX, COUP-TFII, NURR1 and LRH-1) that showed common upregulation in both mRNA and protein levels in the prostatospheroids and castration-relapse VCaP-CRPC xenografts, and overexpression of these orphan NRs could increase cancer stem cell marker expressions and enhance spheroid formation capacity in prostate cancer cells, suggesting that these orphan NRs might perform positive roles in the growth regulation of PCSCs and castration-resistant prostate cancer. Together, our NR expression dataset not only revealed the distinct physiologic status and regulatory roles governed by the networks of specific NRs but also some of these identified orphan NRs could be the potential therapeutic targets for PCSCs or castration-resistant prostate cancer.
['Wang|Zhu|Z|', 'Wu|Dinglan|D|', 'Ng|Chi-Fai|CF|', 'Teoh|Jeremy Yuen-Chun|JY|', 'Yu|Shan|S|', 'Wang|Yuliang|Y|', 'Chan|Franky L|FL|']
D000818:Animals D014408:Biomarkers, Tumor D051837:COUP Transcription Factor II D006801:Humans D008297:Male D016513:Mice, SCID D014411:Neoplastic Stem Cells D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 D057093:Orphan Nuclear Receptors D064129:Prostatic Neoplasms, Castration-Resistant D018160:Receptors, Cytoplasmic and Nuclear D018168:Receptors, Retinoic Acid D018874:Spheroids, Cellular D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
nuclear receptors prostate cancer castration resistance orphan nuclear receptors prostate cancer stem-like cells