ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes

Prostate. 2006 Oct 1;66(14):1474-86. doi: 10.1002/pros.20477.

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.

Conclusion: These findings suggest that AR and ACTR may play important roles in androgen ablation resistance by controlling key cell cycle gene expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / metabolism
  • Animals
  • CDC2-CDC28 Kinases / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cyclin B / genetics
  • Cyclin D1 / genetics
  • Cyclin E / genetics
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Male
  • Mice
  • Neoplasm Transplantation
  • Nuclear Receptor Coactivator 2 / genetics
  • Nuclear Receptor Coactivator 3
  • Promoter Regions, Genetic / physiology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / physiopathology
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transplantation, Heterologous

Substances

  • Androgens
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclin E
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Receptors, Androgen
  • Trans-Activators
  • Cyclin D1
  • Histone Acetyltransferases
  • NCOA3 protein, human
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3
  • CDC2-CDC28 Kinases