title: ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes.
abstract: BACKGROUND
  Co-factor ACTR is frequently overexpressed and/or amplified in multiple types of tumors. The mechanism of its function in prostate cancer (CaP) is still unclear.
  
  
  METHODS
  The effects of ACTR and androgen receptor (AR) depletion on cell proliferation and gene expression and their functions were analyzed in a panel of androgen-dependent and -independent CaP cells and CWR22 xenograft.
  
  
  RESULTS
  ACTR and AR, but not TIF2, are required for proliferation of androgen-dependent and -independent cells, and for tumor growth. While AR depletion inhibited the expression of cyclin D1, cyclin B, and cdc2, ACTR depletion reduced the expression of cyclin E and cdk2. In response to serum stimulation, AR and ACTR are recruited to the corresponding target gene promoters to activate their expression in androgen-independent manner.
  
  
  CONCLUSIONS
  These findings suggest that AR and ACTR may play important roles in androgen ablation resistance by controlling key cell cycle gene expression.
authors.affiliation: UC Davis Cancer Center/Basic Sciences, Department of Biochemistry & Molecular Medicine, University of California at Davis, School of Medicine, Sacramento, California, USA. jxzou@ucdavis.edu
authors.forename: June X
authors.initials: JX
authors.lastname: Zou
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhong
authors.forename: Xu-Bao
authors.initials: XB
authors.lastname: Shi
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Tepper
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Hongwu
authors.initials: H
authors.lastname: Chen
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics; D056921:Nuclear Receptor Coactivator 3; D011401:Promoter Regions, Genetic / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D000728:Androgens; D018797:Cell Cycle Proteins; D019926:Cyclin B; D019927:Cyclin E; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D015534:Trans-Activators; D019938:Cyclin D1; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3; D042846:CDC2-CDC28 Kinases