scholarly journals Molecular basis of androgen resistance in a family with a qualitative abnormality of the androgen receptor and responsive to high-dose androgen therapy.

1991 ◽  
Vol 87 (4) ◽  
pp. 1413-1421 ◽  
Author(s):  
M J McPhaul ◽  
M Marcelli ◽  
W D Tilley ◽  
J E Griffin ◽  
R F Isidro-Gutierrez ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Molecular Basis ◽  
High Dose ◽  
Androgen Therapy ◽  
Androgen Resistance

Androgen Resistance Associated With a Qualitative Abnormality of the Androgen Receptor and Responsive to High Dose Androgen Therapy*

1989 ◽  
Vol 68 (3) ◽  
pp. 578-584 ◽  
Author(s):  
PLACIDO B. GRINO ◽  
ROSARIO F. ISIDRO-GUTIERREZ ◽  
JAMES E. GRIFFIN ◽  
JEAN D. WILSON
Keyword(s):  
Androgen Receptor ◽  
High Dose ◽  
Androgen Therapy ◽  
Androgen Resistance

scholarly journals Dual Functions of SPOP and ERG Dictate Androgen Therapy Responses in Prostate Cancer

2020 ◽  
Author(s):  
Tiziano Bernasocchi ◽  
Geniver El Tekle ◽  
Marco Bolis ◽  
Azzurra Mutti ◽  
Arianna Vallerga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Wild Type ◽  
Driver Genes ◽  
Androgen Therapy ◽  
Cancer Driver ◽  
Cancer Pathways ◽  
Mutation Pattern

Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually-exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP. ERG up-regulates wild type SPOP to dampen androgen receptor (AR) signaling and sustain ERG activity through degradation of the bromodomain histone reader ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG-function and enable oncogenic androgen receptor signaling. This dichotomy regulates the response to therapeutic interventions in the AR pathway. While mutant SPOP renders tumor cells susceptible to androgen deprivation therapies, ERG promotes sensitivity to high-dose androgen therapy and pharmacological inhibition of wild type SPOP. More generally, these results define a distinct class of antagonistic cancer drivers and a blueprint toward their therapeutic exploitation.

scholarly journals Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tiziano Bernasocchi ◽  
Geniver El Tekle ◽  
Marco Bolis ◽  
Azzurra Mutti ◽  
Arianna Vallerga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Therapeutic Interventions ◽  
High Dose ◽  
Wild Type ◽  
Driver Genes ◽  
Androgen Therapy ◽  
Cancer Driver ◽  
Cancer Pathways ◽  
Mutation Pattern

AbstractDriver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP. ERG upregulates wild type SPOP to dampen androgen receptor (AR) signaling and sustain ERG activity through degradation of the bromodomain histone reader ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG-function and enable oncogenic androgen receptor signaling. This dichotomy regulates the response to therapeutic interventions in the AR pathway. While mutant SPOP renders tumor cells susceptible to androgen deprivation therapies, ERG promotes sensitivity to high-dose androgen therapy and pharmacological inhibition of wild type SPOP. More generally, these results define a distinct class of antagonistic cancer drivers and a blueprint toward their therapeutic exploitation.

Androgen Receptor Defects in Patients with Minimal and Partial Androgen Resistance Classified According to a Model of Androgen-Receptor Complex Energy States

1990 ◽  
Vol 33 (2-4) ◽  
pp. 87-94 ◽  
Author(s):  
M. Kaufman ◽  
L. Pinsky ◽  
B. Gottlieb ◽  
M. Schweitzer ◽  
A. Brezezinski ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Complex ◽  
Complex Energy ◽  
Androgen Resistance ◽  
Energy States

Androgen resistance caused by mutations in the androgen receptor gene

1991 ◽  
Vol 5 (14) ◽  
pp. 2910-2915 ◽  
Author(s):  
M. J. McPhaul ◽  
M. Marcelli ◽  
W. D. Tilley ◽  
J. E. Griffin ◽  
J. D. Wilson
Keyword(s):  
Androgen Receptor ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Androgen Resistance

Androgen resistance due to decreased amounts of androgen receptor: A reinvestigation

1990 ◽  
Vol 35 (6) ◽  
pp. 647-654 ◽  
Author(s):  
Placido B. Grino ◽  
James E. Griffin ◽  
Jean D. Wilson
Keyword(s):  
Androgen Receptor ◽  
Androgen Resistance

scholarly journals Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 914
Author(s):  
Po-Fan Hsieh ◽  
Wen-Ping Jiang ◽  
Shih-Yin Huang ◽  
Praveenkumar Basavaraj ◽  
Jin-Bin Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Androgen Receptor ◽  
Molecular Basis ◽  
Fatty Acid Synthase ◽  
Specific Antigen ◽  
Receptor Expression ◽  
Migration And Invasion ◽  
Therapeutic Activity ◽  
Castration Resistant

Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.

Sign in / Sign up

Export Citation Format

Share Document