Glucose-regulated protein 78 modulates cell growth, epithelial–mesenchymal transition, and oxidative stress in the hyperplastic prostate

作者：Xun Fu, Jianmin Liu, Daoquan Liu, Yongying Zhou, Yuhang Guo, Zhen Wang, Shu Yang, Weixiang He, Ping Chen, Xinghuan Wang, Michael E. DiSanto, Xinhua Zhang · 发表于：Cell Death and Disease · 年份：2022 · DOI：10.1038/s41419-022-04522-4 · 被引用次数：30 · 研究领域：Endoplasmic Reticulum Stress and Disease、Connexins and lens biology、Heat shock proteins research

Benign prostatic hyperplasia (BPH) is a chronic condition which mainly affects elderly males. Existing scientific evidences have not completely revealed the pathogenesis of BPH. Glucose-regulated protein 78 (GRP78) is a member of the heat shock protein 70 superfamily, which serves as an important regulator in many diseases. This study aims at elucidating the role of GRP78 in the BPH process. Human prostate tissues, cultured human prostate cell lines (BPH-1 and WPMY-1) and clinical data from BPH patients were utilized. The expression and localization of GRP78 were determined with quantitative real time PCR (qRT-PCR), Western blotting and immunofluorescence staining. GRP78 knockdown and overexpression cell models were created with GRP78 siRNA and GRP78 plasmid transfection. With these models, cell viability, apoptosis rate, as well as marker levels for epithelial-mesenchymal transition (EMT) and oxidative stress (OS) were detected by CCK8 assay, flow cytometry analysis and Western blotting respectively. AKT/mTOR and MAPK/ERK pathways were also evaluated. Results showed GRP78 was localized in the epithelium and stroma of the prostate, with higher expression in BPH tissues. There was no significant difference in GRP78 expression between BPH-1 and WPMY-1 cell lines. In addition, GRP78 knockdown (KD) slowed cell growth and induced apoptosis, without effects on the cell cycle stage of both cell lines. Lack of GRP78 affected expression levels of markers for EMT and OS. Consistently, ...