Shortened isoforms of the androgen receptor are regulated by the cytoprotective heat-shock protein HSPB1 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.


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.


CONCLUSIONS
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.
Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Str., D-17475 Greifswald, Germany, matthias.stope@uni-greifswald.de.
Matthias B
MB
Stope
Juliane
J
Bradl
Stefanie
S
Peters
Andreas
A
Streitbörger
Martin
M
Weiss
Uwe
U
Zimmermann
Reinhard
R
Walther
Christopher H
CH
Lillig
Martin
M
Burchardt
D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D018832:Molecular Chaperones; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C410798:AR protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D020033:Protein Isoforms; D012333:RNA, Messenger; D011944:Receptors, Androgen
Androgen receptor; heat-shock protein HSPB1; isoform; microRNA miR-1