@article{TEXTUAL,
      recid = {8393},
      author = {Kokontis, John M. and Lin, Hui-Ping and Jiang, Shih Sheng  and Lin, Ching-Yu and Fukuchi, Junichi and Hiipakka,  Richard A. and Chung, Chi-Jung and Chan, Tzu-Min and Liao,  Shutsung and Chang, Chung-Ho and Chuu, Chih-Pin},
      title = {Androgen Suppresses the Proliferation of Androgen  Receptor-Positive Castration-Resistant Prostate Cancer  Cells via Inhibition of Cdk2, CyclinA, and Skp2},
      journal = {PLOS ONE},
      address = {2014-10-01},
      number = {TEXTUAL},
      abstract = {<p>The majority of prostate cancer (PCa) patient receiving  androgen ablation therapy eventually develop  castration-resistant prostate cancer (CRPC). We previously  reported that androgen treatment suppresses Skp2 and c-Myc  through androgen receptor (AR) and induced G1 cell cycle  arrest in androgen-independent LNCaP 104-R2 cells, a late  stage CRPC cell line model. However, the mechanism of  androgenic regulation of Skp2 in CRPC cells was not fully  understood. In this study, we investigated the androgenic  regulation of Skp2 in two AR-positive CRPC cell line  models, the LNCaP 104-R1 and PC-3<sup>AR</sup> Cells. The  former one is an early stage androgen-independent LNCaP  cells, while the later one is PC-3 cells re-expressing  either wild type AR or mutant LNCaP AR. Proliferation of  LNCaP 104-R1 and PC-3<sup>AR</sup> cells is not dependent  on but is suppressed by androgen. We observed in this study  that androgen treatment reduced protein expression of Cdk2,  Cdk7, Cyclin A, cyclin H, Skp2, c-Myc, and E2F-1; lessened  phosphorylation of Thr14, Tyr15, and Thr160 on Cdk2;  decreased activity of Cdk2; induced protein level of  p27<sup>Kip1</sup>; and caused G1 cell cycle arrest in  LNCaP 104-R1 cells and PC-3<sup>AR</sup> cells.  Overexpression of Skp2 protein in LNCaP 104-R1 or  PC-3<sup>AR</sup> cells partially blocked accumulation of  p27<sup>Kip1</sup> and increased Cdk2 activity under  androgen treatment, which partially blocked the androgenic  suppressive effects on proliferation and cell cycle.  Analyzing on-line gene array data of 214 normal and PCa  samples indicated that gene expression of Skp2, Cdk2, and  cyclin A positively correlates to each other, while Cdk7  negatively correlates to these genes. These observations  suggested that androgen suppresses the proliferation of  CRPC cells partially through inhibition of Cyclin A, Cdk2,  and Skp2.</p>},
      url = {http://knowledge.uchicago.edu/record/8393},
}