The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F16%3A33159911" target="_blank" >RIV/61989592:15110/16:33159911 - isvavai.cz</a>

Result on the web

<a href="http://erc.endocrinology-journals.org/content/23/6/495.full.pdf+html" target="_blank" >http://erc.endocrinology-journals.org/content/23/6/495.full.pdf+html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/ERC-16-0160" target="_blank" >10.1530/ERC-16-0160</a>

Result language

angličtina

Original language name

The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1

Original language description

Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR)-interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long-term NCOA1 knockdown on processes relevant to metastasis formation. [(3)H]-thymidine incorporation assays revealed a reduced proliferation rate in AR-positive MDA PCa 2b and LNCaP cells upon knockdown of NCOA1, whereas AR-negative PC3 cells were not affected. Furthermore, Boyden chamber assays showed a strong decrease in migration and invasion upon NCOA1 knockdown, independently of the cell line's AR status. In order to understand the mechanistic reasons for these changes, transcriptome analysis using cDNA microarrays was performed. Protein kinase D1 (PRKD1) was found to be prominently up-regulated by NCOA1 knockdown in MDA PCa 2b, but not in PC3 cells. Inhibition of PRKD1 reverted the reduced migratory potential caused by NCOA1 knockdown. Furthermore, PRKD1 was negatively regulated by AR. Immunohistochemical staining of PCa patient samples revealed a strong increase in NCOA1 expression in primary tumors compared with normal prostate tissue, while no final conclusion could be drawn for PRKD1 expression in tumor specimens. Thus, our findings directly associate the AR/NCOA1 complex with PRKD1 regulation and cellular migration and support the concept of therapeutic inhibition of NCOA1 in PCa.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Endocrine Related Cancer

ISSN

1351-0088

e-ISSN

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Volume of the periodical

23

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

495-508

UT code for WoS article

000378753200009

EID of the result in the Scopus database

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