title: Biphasic effect of androgens on prostate cancer cells and its correlation with androgen receptor coactivator dopa decarboxylase.
abstract: The aim of this study was to explore the mechanism underlying the dual effect of androgen on prostate cancer cells and further explore its correlation with dopa decarboxylase (DDC), an androgen receptor (AR) coactivator and a traditional neuroendocrine differentiation (NED) marker. Cell proliferation and cycling after treatment with synthetic nonmetabolizable androgen R1881 was determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method and flow cytometry. Differential gene expression was analyzed by cDNA microarrays. DDC expression during the dual effect of R1881 was further explored with microarray, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and enzyme activity assays. Proliferation of LNCaP cells was inhibited by 1 nM R1881 but stimulated by 0.1 nM R1881. Compared with the untreated cells, 320 (2.26%; 170 up-regulated, 150 down-regulated) and 4608 (32.65%; 2046 up-regulated, 2562 down-regulated) genes were found to be expressed differentially in the 1 nM and 0.1 nM R1881-treated cells, respectively. The results were partially confirmed by RT-PCR and Western blot. The DDC gene was down-regulated in the 1 nM R1881-treated cells and up-regulated in 0.1 nM R1881- and 30 nM hydroxyflutamide-treated cells. The enzymatic activity of DDC in the latter 2 groups was also strengthened. Meanwhile, the NED markers CgA and synaptophysin were not affected by these AR activators. R1881 had a dose-dependent biphasic effect on LNCaP cell proliferation. AR coactivator DDC was respectively down- and up-regulated in high and low concentrations of R1881. DDC up-regulation by exogenous AR activators is not accompanied by up-regulation of definitive NED markers.
authors.affiliation: Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shao
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yue
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Zhang
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Shi
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.forename: Ting-Yi
authors.initials: TY
authors.lastname: Bao
authors.forename: Zeng-Yue
authors.initials: ZY
authors.lastname: Yang
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Yuan
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Shao
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004296:Dopa Decarboxylase / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms; D016196:S Phase / Q000187:drug effects
chemical_list: D000728:Androgens; D015741:Metribolone; D004296:Dopa Decarboxylase