Purpose: Steroid hormones, particularly androgens, are suspected to have a major role in prostate carcinogenesis. Since androgen receptor mediates androgenic effects on cells and recent studies suggest that the androgen receptor gene is a putative prostate cancer susceptibility locus, we screened the coding region of the androgen receptor gene for germline mutations using the genomic DNA of patients with prostate cancer.
Materials And Methods: DNA samples from 38 patients with early onset prostate cancer and 36 from Finnish prostate cancer families showing no male-to-male transmission of prostate cancer were analyzed for mutations in the androgen receptor gene using single strand conformation polymorphism analysis and subsequent sequencing.
Results: R726L substitution in the hormone binding region of androgen receptor was found in 1 prostate cancer family but no previously uncharacterized germline mutations were detected.
Conclusions: Our results indicate that constitutional androgen receptor mutations explain only a small fraction of familial and early onset prostate cancer cases in Finland.
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http://dx.doi.org/10.1097/01.ju.0000089774.99728.ef | DOI Listing |
Bioengineering (Basel)
January 2025
Department of Pathology, Stavanger University Hospital, 4011 Stavanger, Norway.
A subset of triple-negative breast cancer (TNBC) expresses the androgen receptor (AR), but thresholds for AR positivity and its clinical significance vary. We hypothesize that objective assessment outperforms subjective methods, and that high AR negatively impacts prognosis. In a population-based TNBC cohort ( = 198) with long follow-up (4-383 months), AR expression was evaluated via subjective scoring (AR-Manual) and automated digital image analysis (AR-DIA).
View Article and Find Full Text PDFJCEM Case Rep
February 2025
University of Utah Health, Division of Endocrinology, Salt Lake City, UT 84108, USA.
Glucocorticoid resistance syndrome (GRS) is caused by inactivating pathogenic variants in the glucocorticoid receptor gene . Reduced glucocorticoid receptor signaling leads to decreased tissue sensitivity to cortisol and resultant biochemical hypercortisolism without the classic clinical features of Cushing syndrome. Patients variably present with signs and symptoms of mineralocorticoid and androgen excess from ACTH overstimulation of the adrenal cortex.
View Article and Find Full Text PDFEur Urol
January 2025
Department of Oncology, City of Hope Cancer Center, Goodyear, AZ, USA.
Background And Objective: Selection of patients harboring mutations in homologous recombination repair (HRR) genes for treatment with a PARP inhibitor (PARPi) is challenging in metastatic castration-resistant prostate cancer (mCRPC). To gain further insight, we quantitatively assessed the differential efficacy of PARPi therapy among patients with mCRPC and different HRR gene mutations.
Methods: This living meta-analysis (LMA) was conducted using the Living Interactive Evidence synthesis framework.
J Med Chem
January 2025
State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
The ligand-binding pocket of the androgen receptor (AR) is the targeting site of all clinically used AR antagonists. However, various drug-resistant mutations emerged in the pocket. We previously reported a new targeting site at the dimer interface of AR (dimer interface pocket) and identified a novel antagonist M17-B15 that failed in oral administration.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
January 2025
Laboratory of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, 04039-032, Brazil. Electronic address:
The aims of this study were to investigate the localization of non-phosphorylated β‑catenin and Galectin-3 (GAL-3), the regulation of the expression of both proteins by activation of estrogen receptors (ERs) and their role in tumorigenic characteristics of androgen-independent prostate cancer DU-145 cells. DU-145 cells were cultured in the absence (control), and presence of 17β-estradiol (E2). Cells were also untreated or pre-treated with the inhibitor of GAL‑3, VA03, or with a compound that disrupts the complex β-catenin-TCF/LEF transcription factor, PKF 118-310.
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