title: Aging up-regulates ARA55 in stromal cells, inducing androgen-mediated prostate cancer cell proliferation and migration.
abstract: Stromal cells in the peripheral zone (PZ) of the prostate from older males (PZ-old) could significantly promote Prostate cancer (PCa) growth compared with stromal cells from young males (PZ-young). But the mechanism is still unknown. In the co-culture system with PZ-old cells, Pc3/Du145 cells showed advanced proliferation and migration after Dihydrotestosterone (DHT) incubation, but DHT didn't show the similar effect in PZ-young co-culture system. Also, higher androgen/AR signal pathway activity and AR-related cytokines secretion (FGF-2, KGF, IGF-1) were found in PZ-old cells. As AR exprssison was equivalent in PZ-old and PZ-young cells, we focused on Androgen receptor associated protein-55(ARA55), a stromal-specific androgen receptor (AR) coactivator. ARA55 expression was higher in PZ-old cells compared with PZ-young cells in vitro. After knocking down ARA55 expression in PZ-old cells, the PCa growth- promoting effect from the PZ-old cells was diminished, which may be explained by the decreased the progressive cytokines secretion (FGF-2, KGF, IGF-1) from PZ-old stromal cells. In vivo, the consistent results were also found: PZ-old cells promoted prostate cancer cells growth, but this effect receded when knocking down ARA55 expression in PZ-old cells. From our study, we found PZ stromal cells presented age-related effects in proliferation and migration of prostate cancer cells in the androgen/AR dependent manner. As aging increased, more ARA55 were expressed in PZ stromal cells, leading to more sensitive androgen/androgen receptor (AR) signal pathway, then constituting a more feasible environment to cancer cells.
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Di
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. jyf_123@163.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China. hanbm@163.com.
authors.forename: Bangmin
authors.initials: B
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines; D004195:Disease Models, Animal; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000728:Androgens; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D011944:Receptors, Androgen; C490351:TGFB1I1 protein, human
keywords: ARA55; Aging; Androgen receptors; Prostate cancer; Stromal cells