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Anticancer Res. 2013 Nov;33(11):4921-6.

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.

Author information

1
Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Str., D-17475 Greifswald, Germany, matthias.stope@uni-greifswald.de.

Abstract

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.

KEYWORDS:

Androgen receptor; heat-shock protein HSPB1; isoform; microRNA miR-1

PMID:
24222130
[Indexed for MEDLINE]

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