Steroid ligands, the forgotten triggers of nuclear receptor action; implications for acquired resistance to endocrine therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F21%3A00013523" target="_blank" >RIV/75010330:_____/21:00013523 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11140/21:10426631
Result on the web
<a href="https://clincancerres.aacrjournals.org/content/27/14/3980" target="_blank" >https://clincancerres.aacrjournals.org/content/27/14/3980</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/1078-0432.CCR-20-4135" target="_blank" >10.1158/1078-0432.CCR-20-4135</a>
Alternative languages
Result language
angličtina
Original language name
Steroid ligands, the forgotten triggers of nuclear receptor action; implications for acquired resistance to endocrine therapy
Original language description
Purpose: There is strong epidemiologic evidence indicating that estrogens may not be the sole steroid drivers of breast cancer. We hypothesize that abundant adrenal androgenic steroid precursors, acting via the androgen receptor (AR), promote an endocrine-resistant breast cancer phenotype. Experimental Design: AR was evaluated in a primary breast cancer tissue microarray (n = 844). Androstenedione (4AD) levels were evaluated in serum samples (n = 42) from hormone receptor-positive, postmenopausal breast cancer. Levels of androgens, progesterone, and estradiol were quantified using LC/MS-MS in serum from age- and grade-matched recurrent and nonrecurrent patients (n = 6) before and after aromatase inhibitor (AI) therapy (>12 months). AR and estrogen receptor (ER) signaling pathway activities were analyzed in two independent AI-treated cohorts. Results: AR protein expression was associated with favorable progression-free survival in the total population (Wilcoxon, P < 0.001). Pretherapy serum samples from breast cancer patients showed decreasing levels of 4AD with age only in the nonrecurrent group (P < 0.05). LC/MS-MS analysis of an AI-sensitive and AI-resistant cohort demonstrated the ability to detect altered levels of steroids in serum of patients before and after AI therapy. Transcriptional analysis showed an increased ratio of AR:ER signaling pathway activities in patients failing AI therapy (t test P < 0.05); furthermore, 4AD mediated gene changes associated with acquired AI resistance. Conclusions: This study highlights the importance of examining the therapeutic consequences of the steroid microenvironment and demonstrable receptor activation using indicative gene expression signatures.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/NV17-28470A" target="_blank" >NV17-28470A: Importance of oxysterol signaling for endocrine therapy of breast carcinoma</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Cancer Research
ISSN
1078-0432
e-ISSN
1557-3265
Volume of the periodical
27
Issue of the periodical within the volume
14
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
3980-3989
UT code for WoS article
000674703200022
EID of the result in the Scopus database
2-s2.0-85110067421