The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer

• DOI: 10.1186/s12964-022-00979-0
• Publication Date: 2022-11-14T11:03:03Z
• Authors: Lei Tian; Yanfei Peng; Kuo Yang; Jiasong Cao; Xiaoling Du; Zhixian Liang; Jiandang Shi; Ju Zhang
• Keywords: Bicalutamide; Signalling

Bicalutamide is a nonsteroidal antiandrogen widely used as first-line clinical treatment for advanced prostate cancer (PCa). Although patients initially show effective responses to bicalutamide treatment, resistance frequently occurs and leads the development of castration-resistant PCa (CRPC). This research investigated roles oestrogen receptor α (ERα)-nuclear factor E2-related 2 (NRF2) signalling pathway in cells.We performed bioinformatic analysis immunohistochemical staining on normal cancerous tissue evaluate ERα NRF2 expression their correlation. Gene localization cell lines were further using real-time reverse transcription PCR/Western blotting immunofluorescence staining. We treated cells with ER inhibitor tamoxifen luciferase reporter assays chromatin immunoprecipitation (ChIP) understand ERα-dependent expression. Overexpression knockdown explore potential role ERα-NRF2 axis found that was positively correlated higher human CRPC tissues than primary tissues. Treatment or increased well target genes lines. These effects blocked by pretreatment tamoxifen. ChIP demonstrated directly binds response element (ERE) promoter. binding led transcriptional activity assay. Activation resistance-related genes. Inhibition this downregulated inhibited proliferation migration interaction between showing direct ERE promoter under treatment. contributes cells, suggesting therapeutic CRPC. Video Abstract.