The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
FD - Onkologie a hematologie
OECD FORD obor
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Návaznosti výsledku
Projekt
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Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2016
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Endocrine Related Cancer
ISSN
1351-0088
e-ISSN
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Svazek periodika
23
Číslo periodika v rámci svazku
6
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
14
Strana od-do
495-508
Kód UT WoS článku
000378753200009
EID výsledku v databázi Scopus
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