Androgen receptor mediates the reduced tumor growth, enhanced androgen responsiveness, and selected target gene transactivation in a human prostate cancer cell line.
The growth and development of the prostate gland are regulated by the androgen and the androgen receptor (AR). Despite our molecular understanding of the roles of the AR regulating; a downstream target gene transcription, the direct or indirect (stromally mediated) actions of the androgen in controlling prostate cell growth and differentiation are still unclear. In this report, an invasive; and metastatic human prostate tumor cell line, androgen-repressed human prostate cancer cell line (ARCaP), either transduced with wild-type human AR (hAR) or a control neomycin-resistant plasmid DNA, was used to evaluate the direct role of AR in regulating prostate tumor cell growth and gene transcription. Results showed that: (a) introduction of wild-type hAR to ARCaP cells restored positive androgen regulation of prostate tumor cell growth in vitro through an enhanced cell-cycle progression from G(0)/G(1) to S and G(2)-M phases; (b) hAR was shown to transactivate glucocorticoid-responsive element but not prostate-specific antigen promoter-directed reporter gene expression; and (c) hAR-transduced ARCaP cells exhibited reduced growth, invasion, and migratory behavior in vitro and tumor growth in vivo. These results suggest that the introduction of hAR into the invasive human prostate cancer ARCaP cell line restored its androgen-regulated cell growth, decreased the rate of tumor growth, and selectively activated AR target gene expression. These cellular functions in response to androgen are commonly associated with increased differentiation of prostate epithelial cells.
Cinar
B
B
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Koeneman
K S
KS
Edlund
M
M
Prins
G S
GS
Zhau
H E
HE
Chung
L W
LW
D000728:Androgens / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D045165:Testosterone Congeners / Q000494:pharmacology; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D011944:Receptors, Androgen; D045165:Testosterone Congeners; D015741:Metribolone