title: The co-regulators SRC-1 and SMRT are involved in interleukin-6-induced androgen receptor activation.
abstract: BACKGROUND
  The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation.
  
  
  METHODS
  The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system. The impacts of IL-6 on the association of the AR with SRC-1 and SMRT were investigated using the mammalian two-hybrid assay.
  
  
  RESULTS
  IL-6 increased the proliferation of LNCaP cells with maximal induction at 50 ng/mL. The AR-SRC-1interaction was enhanced by IL-6, with maximal induction at the concentration of 50 ng/mL (P<0.05). IL-6 decreased the AR-SMRT interaction and a marked reduction was detected at 50 ng/mL (P<0.05).
  
  
  CONCLUSIONS
  IL-6 enhances LNCaP cells proliferation, which suggests that IL-6 might cause AR-positive prostate cancer growth through activation of the AR. The mechanism of IL-6-induced AR activation is mediated through enhancing AR-SRC-1 interaction and inhibiting AR-SMRT interaction. We have shown a significant role for SRC-1 and SMRT in modulating IL-6-induced AR transactivation.
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ju
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ding
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Ge
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qiao-Mei
authors.initials: QM
authors.lastname: Shi
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zhou
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Zhang
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Zhang
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Yu
authors.affiliation: School of Public Health, Xuzhou Medical College, Xuzhou, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C539130:NCOR2 protein, human; D009363:Neoplasm Proteins; D056985:Nuclear Receptor Co-Repressor 2; D011944:Receptors, Androgen; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1
keywords: androgen receptor; interleukin-6; silencing mediator for retinoid and thyroid hormone receptors; steroid receptor coactivator-1