title: Increased PrLZ-mediated androgen receptor transactivation promotes prostate cancer growth at castration-resistant stage.
abstract: Most advanced prostate cancers (PCa) will develop into the castration-resistant stage following androgen deprivation therapy, yet the molecular mechanisms remain unclear. In this study, we found PrLZ, a newly identified Prostate Leucine Zipper gene that is highly expressed in PCa could interact with the androgen receptor (AR) directly leading to enhance AR transactivation in the castration-resistant condition. PrLZ might enhance AR transactivation via a change of AR conformation that leads to promotion of AR nuclear translocation and suppression of AR degradation via modulating the proteasome pathway, which resulted in increased prostate-specific antigen expression and promoted PCa growth at the castration-resistant stage. Clinical PCa sample survey from same-patient paired specimens found increased PrLZ expression in castration-resistant PCa following the classical androgen deprivation therapy. Targeting the AR-PrLZ complex via ASC-J9® or PrLZ-siRNA resulted in suppression of PCa growth in various human PCa cells and in vivo mouse PCa models. Together, these data not only strengthen PrLZ roles in the transition from androgen dependence to androgen independence during the castration-resistant stage, but they may also provide a new potential therapy to battle PCa at the castration-resistant stage.
authors.affiliation: Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University,  Xi'an 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Hongjun
authors.initials: H
authors.lastname: Xie
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Ye
authors.initials: Y
authors.lastname: Gao
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Leiya
authors.initials: L
authors.lastname: Fang
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Xingfa
authors.initials: X
authors.lastname: Chen
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Luke S
authors.initials: LS
authors.lastname: Chang
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D019556:COS Cells; D002369:Castration; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous; D020798:Two-Hybrid System Techniques
chemical_list: C410798:AR protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; C114751:TPD52 protein, human; D005982:Glutathione Transferase; D046988:Proteasome Endopeptidase Complex