Characterization of prostate cancer DU145 cells expressing the recombinant androgen receptor.
Prostate cancer (PC) develops as a consequence of abnormal androgenic stimulation. Unfortunately, most of the PC cell lines are androgen independent (like DU145), or express mutated forms of androgen receptor (AR). We have produced and characterized a new stably transfected PC line expressing the AR (DU145-AR). Untreated DU145-AR cells showed a lower proliferation rate than mock transfected cells, but responded to testosterone treatment. PSA mRNA, undetectable in mock DU145 cells, was present and upregulated by testosterone in DU145-AR. About 5% of DU 145-AR cells showed modification of morphology and enriched of f-actin after testosterone treatment. Moreover, in DU145-AR plasminogen activator (PA) activity and secreted urokinase type plasminogen activator (uPA) protein were lower than in AR negative cells; again testosterone induced PA activity and uPA protein only in DU145-AR. These results indicate that, in general, the effects of unactivated AR is to suppress function(s) in DU145 cells and the addition of testosterone restores the normal properties associated with the untransfected cells. Some of the effects described may thus be mediated by a ligand-independent activation of AR in DU145 cells.
Scaccianoce
Eugenia
E
Centre for Endocrinological Oncology, Institute of Endocrinology, University of Milan, Italy.
Festuccia
Claudio
C
Dondi
Donatella
D
Guerini
Vittoria
V
Bologna
Mauro
M
Motta
Marcella
M
Poletti
Angelo
A
D015139:Blotting, Southern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D010960:Plasminogen Activators / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013739:Testosterone / Q000494:pharmacology; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D011944:Receptors, Androgen; D011994:Recombinant Proteins; D013739:Testosterone; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D017430:Prostate-Specific Antigen