期刊
ONCOLOGY REPORTS
卷 35, 期 1, 页码 584-592出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.4362
关键词
lysine-specific demethylase 1; androgen-independent transition; human prostate cancer; LNCaP cells; androgen receptor; p53
类别
资金
- National Natural Science Foundation of China [30973008, 81272847]
- Program for New Century Excellent Talents in University [NCET-13-0239]
Lysine-specific demethylase 1 (LSD1) is the first defined histone demethylase, and was found to be closely correlated with the development and progression of various types of cancers, including prostate cancer (PCa). Previous research suggests that LSD1 is closely related with cell proliferation, angiogenesis, migration and invasion in PCa. However, it remains to be elucidated whether LSD1 is correlated with androgen-independent (AI) transition of PCa under androgen-ablated conditions. The present study aimed to investigate the correlation of LSD1 expression with AT transition of human androgen-dependent PCa LNCaP cells. Our data showed that LSD1 was overexpressed in human PCa specimens and in AI PCa LNCaP-AI cells, which weie established through a three-month continuous culture of LNCaP cells in androgen-deprived medium. Under androgen-deprived conditions, LNCaP-AI cells grew perfectly with less apoptosis and G(0)/G(1), cell cycle arrest. Overexpression of LSD1 protected the LNCaP cells from androgen deprivation-induced apoptosis and G(0)/G(1), arrest, while knockdown of LSD1 drove LNCaP-AI cells into a higher rate of apoptosis and G(0)/G(1) arrest. Furthermore, LSD1 was found to regulate the androgen receptor (AR) and p53 signaling pathways via demethylation, subsequently influencing apoptosis and cell cycle progression. These findings revealed that overexpression of LSD1 promoted AT transition of PCa LNCaP cells under androgen-ablated conditions via activation of the AR signaling pathway and suppression of the p53 signaling pathway.
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