Prostate specific antigen expression does not necessarily correlate with prostate cancer cell growth.
OBJECTIVE
The antiproliferative effects of pharmacological agents used for androgen ablative therapy in prostate cancer, including goserelin, bicalutamide and cyproterone acetate (Fluka Chemie, Buchs, Switzerland), were tested in vitro. It was determined whether they affected prostate specific antigen mRNA and protein expression independent of growth inhibition.


METHODS
Goserelin, bicalutamide (AstraZeneca, Zug, Switzerland) and cyproterone acetate were added to prostate specific antigen expressing, androgen dependent LNCaP and androgen independent C4-2 cell line (Urocor, Oklahoma City, Oklahoma) cultures. Proliferation was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay (Roche, Mannheim, Germany). Prostate specific antigen mRNA expression was assessed by quantitative real-time polymerase chain reaction. Secreted prostate specific antigen protein levels were quantified by microparticle enzyme-immunoassay.


RESULTS
Goserelin inhibited cell growth and prostate specific antigen protein secretion in LNCaP and C4-2 cells. Prostate specific antigen mRNA expression was not decreased. Bicalutamide did not affect cell growth or prostate specific antigen mRNA expression in LNCaP or C4-2 cells, although it significantly decreased prostate specific antigen protein secretion in LNCaP and to a lesser extent in C4-2 cells. Cyproterone acetate decreased the growth of C4-2 but not of LNCaP cells. It did not affect prostate specific antigen mRNA or protein expression in either cell line.


CONCLUSIONS
Prostate specific antigen expression does not necessarily correlate with cell growth. Without a substantial effect on cell growth bicalutamide lowers prostate specific antigen synthesis, whereas cyproterone acetate decreases cell growth with no effect on prostate specific antigen secretion. Prostate specific antigen expression may be influenced by growth inhibition but also by altered mRNA and protein levels depending on the agent, its concentration and the cell line evaluated. For interpreting clinical trials prostate specific antigen is not necessarily a surrogate end point marker for a treatment effect on prostate cancer cell growth.
Peternac
Daniel
D
Department of Urology, University of Bern, Inselspital, 3010 Bern, Switzerland.
Klima
Irena
I
Cecchini
Marco G
MG
Studer
Urs E
UE
Thalmann
George N
GN
D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017373:Cyproterone Acetate / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis; D017273:Goserelin / Q000494:pharmacology; D006801:Humans; D008297:Male; D009570:Nitriles; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D009570:Nitriles; D012333:RNA, Messenger; D014105:Tosyl Compounds; D017273:Goserelin; D017373:Cyproterone Acetate; C053541:bicalutamide; D017430:Prostate-Specific Antigen