Upregulation of PACE4 in prostate cancer is not dependent on E2F transcription factors.

Abstract

Recent studies in prostate cancer have identified PACE4, a proprotein convertase enzyme, as an emerging therapeutic target. Inhibition of PACE4-altCT, an oncogenic isoform of PACE4, using molecular or pharmacological approaches results in decreased cell proliferation and tumor progression in xenograft models. Although several validations have confirmed PACE4-altCT as a novel therapeutic target, the transcriptional regulation of PACE4 isoforms and mechanism of action remain a challenge. Previously, it has been reported that the human PACE4 promoter possesses potential binding sites for the E2F family of transcription factors, all of which are involved in cell cycle regulation and synthesis of DNA in mammalian cells. Therefore, we attempted to conduct in-depth evaluation of E2Fs on PACE4 and PACE4 isoform expression in prostate cancer. We conducted in vitro molecular silencing studies in various prostate cancer cell lines and determined the change in PACE4 expression levels. The results clearly show that the E2Fs alone do not alter PACE4 expression.