Genetic alterations and changes in expression of histone demethylases in prostate cancer
Version of Record online: 1 FEB 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 70, Issue 8, pages 889–898, 1 June 2010
How to Cite
Suikki, H. E., Kujala, P. M., Tammela, T. L.J., van Weerden, W. M., Vessella, R. L. and Visakorpi, T. (2010), Genetic alterations and changes in expression of histone demethylases in prostate cancer. Prostate, 70: 889–898. doi: 10.1002/pros.21123
- Issue online: 20 APR 2010
- Version of Record online: 1 FEB 2010
- Manuscript Accepted: 15 DEC 2009
- Manuscript Received: 29 OCT 2009
- Academy of Finland
- Cancer Society of Finland
- Reino Lahtikari Foundation, the Competitive Research Funding of the Pirkanmaa Hospital District
- Sigrid Juselius Foundation
- European Union (PRIMA). Grant Number: LSHC-CT-2004-504587
- The Richard M Lucas Foundation
- prostatic neoplasia;
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.
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.
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.
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. © 2010 Wiley-Liss, Inc.