Genetic Alterations and Changes in Expression of Histone Demethylases in Prostate Cancer

BACKGROUND. Historic 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 m RNA 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. Prostate 70: 889-898, 2010. (C) 2010 Wiley-Liss, Inc.