Combinatorial Transcription Regulation of Oncogene CDC6 in Androgen-Sensitive Prostate Cancer Cells

Abstract

Previous studies showed that CDC6 gene transcription is mainly regulated by E2F transcription factors. We recently reported [1] a novel regulatory mechanism of aberrant CDC6 gene transcription in androgen-responsive prostate cancer (PCa) cells where FOXM1 transcription factor positively regulates CDC6 gene transcription and DNA replication. In addition to direct binding to the CDC6 promoter, FOXM1 regulates CDC6 gene transcription by elevating AR gene expression. Furthermore, FOXM1 and AR collaborate to regulate CDC6 gene transcription in a cell cycle-dependent manner. Supporting the significance of this mechanism, siomycin A, a proteasome inhibitor known to inhibit FOXM1 expression and activity, inhibited PCa cell proliferation, and the effect of siomycin A was additive to that of bicalutamide, an antiandrogen commonly used to treat PCa patients.