LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models.

ABSTRACT:

Background

Castrate resistant prostate cancer (CRPC) is often driven by constitutively active forms of the androgen receptor such as the V7 splice variant (AR-V7) and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. The lysine demethylase LSD1 is a co-activator of the wild type androgen receptor and a potential therapeutic target in hormone sensitive prostate cancer. We evaluated whether LSD1 could also be therapeutically targeted in CRPC models driven by AR-V7.

Methods

We utilised cell line models of castrate resistant prostate cancer through over expression of AR-V7 to test the impact of chemical LSD1 inhibition on AR activation. We validated findings through depletion of LSD1 expression and in prostate cancer cell lin

SUBMITTER: Regufe da Mota S 

PROVIDER: S-EPMC5941811 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature