FOXP1 KNOCKDOWN ALTERS ANDROGEN REGULATED TRANSCRIPTIONAL EXPRESSION MAKING PROSTATE CANCER LNCAP MORE AGGRESSIVE

Abstract

Prostate cancer has developed ways to become resistant to current therapies due to the androgen receptor’s complex means of activation. The androgen receptor (AR) spearheads prostate cancer’s capability to progress as it has many splice variants and regulatory mechanisms. Forkhead box protein P1 (FOXP1) regulates the androgen receptor and may influence tumor proliferation and hormone responsiveness in prostate cancer. We therefore investigate if FOXP1 regulates certain subsets of androgen dependent genes. Knockdown of FOXP1 is achieved through lentiviral transduction of shRNA FOXP1-1 (shFOXP1-1). Immunofluorescence shows down-regulation of FOXP1 is associated with increased activation and localization of nuclear AR. This knockdown results in the upregulation of the transcription factor, NK3 Homeobox 1 (NKX3.1), but not all AR responsive genes. This suggests FOXP1 is involved in other androgen responsive transcription pathways. Furthermore, LNCaP with FOXP1 knockdown induced increased cell proliferation and survival compared to wild type. This study further establishes FOXP1’s importance as a regulator of AR and its capability to regulate androgen responsive proliferative genes.