Comparison of gene expression in LNCaP prostate cancer cells after treatment with bicalutamide or 5-alpha-reductase inhibitors.
BACKGROUND
Androgen deprivation is the preferred treatment for disseminated prostate cancer. However, it mostly leads to the development of incurable androgen-independent disease. The aim of the present study was to compare gene expression changes that occur after treatment with either the antiandrogen bicalutamide or the 5-alpha-reductase inhibitors finasteride (MK906) and MK386.


METHODS
LNCaP cells of low passages were treated with MK906 and MK386 at 5 microM each or with bicalutamide at 10 microM for 48 h. In these cultures we analyzed the expression of 22,500 transcripts on the Affymetrix Human U133+ 2.0 GeneChip platform. Gene expression was verified by real-time quantitative Taqman PCR.


RESULTS
Our studies revealed 312 differentially regulated genes upon bicalutamide treatment and 68 differentially regulated genes upon treatment with the 5-alpha-reductase inhibitors. There were 35 genes equally regulated by both drugs. This subset of genes included those with the highest fold change in both treatment groups. In the subset KlK2, TMPRSS2, TRGC2, PMEPA1 and TM4SF1 were downregulated, whereas EGR1, DDC and OPRK1 were upregulated.


CONCLUSIONS
A cohort of interesting genes that are differentially expressed after androgen withdrawal could be found in this study. Investigation into these genes could contribute to a better understanding of antiandrogen treatment and development of androgen-independent prostate cancer.
Bühler
Patrick
P
Department of Urology, Experimental Research Group, University of Freiburg, Freiburg, Germany.
Fischer
Thomas
T
Wolf
Philipp
P
Gierschner
Dorothee
D
Schultze-Seemann
Wolfgang
W
Wetterauer
Ulrich
U
Elsässer-Beile
Ursula
U
D000813:Anilides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001378:Azasteroids / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014105:Tosyl Compounds / Q000494:pharmacology*
C090665:4,7beta-dimethyl-4-azacholestan-3-one; D000813:Anilides; D000970:Antineoplastic Agents; D001378:Azasteroids; D004791:Enzyme Inhibitors; D009570:Nitriles; D014105:Tosyl Compounds; D018120:Finasteride; C053541:bicalutamide; D042944:Cholestenone 5 alpha-Reductase