title: NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer.
abstract: Castration resistance is a major issue during castration therapy for prostate cancer and thus more effective treatment are needed for castration-resistant prostate cancer (CRPC). NDRG2 (N-Myc downstream regulated gene 2), a recently identified tumor suppressor, was previously shown to inhibit the proliferation and invasion of prostate cancer, but whether NDRG2 is involved in CRPC remains to be known. Because androgen receptor (AR) axis plays an important role in castration resistance, we evaluate the role of NDRG2 in AR signaling and CRPC. Immunohistochemistry examination of prostate cancer tissues demonstrated that the expression of NDRG2 is negatively correlated with that of AR and c-Myc. Furthermore, AR negatively regulates NDRG2, as well as alters levels of c-Myc and prostate specific antigen (PSA). Forced expression of NDRG2 significantly inhibits the in vitro growth of androgen-dependent and castration-resistant prostate cancer cells; this was accompanied by alterations in PSA, but not by those of AR and c-Myc. Finally, by mimicking castration therapy in a xenograft mouse model, we showed that lentivirus-mediated NDRG2 overexpression efficiently overcomes castration resistance. Thus, by acting as a negative regulator downstream of AR, NDRG2 may emerge as a potential therapy molecule for CRPC.
authors.affiliation: a State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology ; the Fourth Military Medical University ; Xi'an , China.
authors.forename: Chuigong
authors.initials: C
authors.lastname: Yu
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Ruixiao
authors.initials: R
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000728:Androgens; C466228:NDRG2 protein, human; D016271:Proto-Oncogene Proteins c-myc; D011944:Receptors, Androgen; D025521:Tumor Suppressor Proteins
keywords: AR; AR, Androgen Receptor; CRPC, Castration-Resistant Prostate Cancer; DHT, Dihydrotestosterone; NDRG2; NDRG2, N-Myc Downstream Regulated Gene 2; PC, Prostate Cancer; c-Myc; castration resistance; lentivirus