E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells.
OBJECTIVE
Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize.


METHODS
In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth.


RESULTS
Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP.


CONCLUSIONS
Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients.
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Kohei
K
Koyama
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Kiyoshi
K
Takahara
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Teruo
T
Inamoto
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Naokazu
N
Ibuki
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Koichiro
K
Minami
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Hirofumi
H
Uehara
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Kazumasa
K
Komura
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Takeshi
T
Nishida
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Takeshi
T
Sakamoto
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Hajime
H
Hirano
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Hayahito
H
Nomi
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Satoshi
S
Kiyama
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Haruhito
H
Azuma
Castrate-resistant disease; Prostate cancer