Genetic alterations and changes in expression of histone demethylases in prostate cancer.
BACKGROUND
Histone demethylases LSD1, JHDM2A, and GASC1 have been suggested to function as androgen receptor co-activators, and to be involved in prostate cancer (PC) progression. We aim to identify genetic alterations and changes in expression of these genes in PC.


METHODS
PC cell lines, xenografts as well as clinical specimens were screened for mutations using denaturating high-performance liquid chromatography and sequencing, and for expression alterations by using quantitative RT-PCR and immunohistochemistry.


RESULTS
Only known single nucleotide polymorphisms, but no mutations, were found in these genes. JHDMA2 mRNA expression was slightly increased (P < 0.05) in PC compared with benign prostate hyperplasia (BPH), whereas the expression of GASC1 was slightly higher (P < 0.05) in castration-resistant PC (CRPC) compared with untreated PC or BPH. The mRNA expression of LSD1 was not altered in PC. The expression of LSD1 protein was somewhat, although not statistically significantly (P = 0.0521) lower in CRPC compared with untreated PC. In prostatectomy specimens, the level of LSD1 protein expression was associated with low pT-stage (P = 0.0402), but not with Gleason score or progression-free survival.


CONCLUSIONS
As no genetic alterations and only very modest expression changes were found, it is unlikely that LSD1, JHDM2A, or GASC1 play a major role in the progression of PC.
Suikki
Hanna E
HE
Institute of Medical Technology, University of Tampere, Tampere, Finland.
Kujala
Paula M
PM
Tammela
Teuvo L J
TL
van Weerden
Wytske M
WM
Vessella
Robert L
RL
Visakorpi
Tapio
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D020022:Genetic Predisposition to Disease / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D046888:Tissue Array Analysis
C413655:KDM4C protein, human; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C530247:KDM3A protein, human; C495195:KDM1A protein, human