Shortened Isoforms of the Androgen Receptor Are Regulated by the Cytoprotective Heat-shock Protein HSPBI and the Tumor-suppressive MicroRNA miR-1 in Prostate Cancer Cells

Background: Shortened, constitutively active androgen receptor (AR) isoforms have been characterized and linked to tumor progression and chemoresistance in prostate cancer (PCa). We examined the regulation of shortened AR isoforms by a newly-identified AR regulatory signaling pathway involving heat-shock protein HSPB1 and microRNA miR-1. Materials and Methods: HSPB1 and miR-1 were modulated by overexpression and knock-down approaches utilizing the model PCa system, 22Rv1. Subsequently, AR isoform expression levels were quantified by western blot analysis. Results: HSPB1 was identified as an inducer and miR-1 as an inhibitor of AR variants, with no detectable discrimination between long and short AR isoform regulation. Conclusion: In 22Rv1 cells, all AR isoforms were co-regulated by the cytoprotective factor HSPB1 and the tumor suppressor miR-1. Notably, our data provide evidence that HSPB1 inhibition is able to target expression of long as well as of short AR isoforms.