Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F16%3A00065541" target="_blank" >RIV/00159816:_____/16:00065541 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.18632/oncotarget.10926" target="_blank" >http://dx.doi.org/10.18632/oncotarget.10926</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.10926" target="_blank" >10.18632/oncotarget.10926</a>

Result language

angličtina

Original language name

Critical role of androgen receptor level in prostate cancer cell resistance to new generation antiandrogen enzalutamide

Original language description

Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of metastatic castration resistant prostate cancer. However, clinical application revealed that 30 to 40% of patients acquire resistance after a short period of treatment. Currently, the molecular mechanisms underlying such resistances are not completely understood, partly due to a lack of model systems. In the present study we established three different cellular models of enzalutamide resistance including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress wild-type AR, as well as a cell which has been adapted to long term androgen ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of cultivation, sustained growth in the presence of enzalutamide was achieved. When compared to controls, resistant cells exhibit significantly decreased sensitivity to enzalutamide as measured with 3[H]thymidine incorporation and WST assay. Moreover, these cell models exhibit partly re-activated AR signaling despite presence of enzalutamide. In addition, we show that enzalutamide resistant cells are insensitive to bicalutamide but retain considerable sensitivity to abiraterone. Mechanistically, enzalutamide resistance was accompanied by increased AR and AR-V7 mRNA and protein expression as well as AR gene amplification, while no additional AR mutations have been identified.

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

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

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

Name of the periodical

Oncotarget

ISSN

1949-2553

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

37

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

59781-59794

UT code for WoS article

000387153900080

EID of the result in the Scopus database

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