ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes.
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.
Zou
June X
JX
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
Zhong
Zhenyu
Z
Shi
Xu-Bao
XB
Tepper
Clifford G
CG
deVere White
Ralph W
RW
Kung
Hsing-Jien
HJ
Chen
Hongwu
H
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
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