scholarly journals Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naïve prostate cancer and are elevated in castration-resistant disease

2013 ◽  
Vol 20 (3) ◽  
pp. 403-413 ◽  
Author(s):  
Tobias Zellweger ◽  
Susanne Stürm ◽  
Silvia Rey ◽  
Inti Zlobec ◽  
Joel R Gsponer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Hormone Receptors ◽  
Expression Profiles ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Poor Overall Survival ◽  
Castration Resistant

Patients with advanced prostate cancer (PC) are usually treated with androgen withdrawal. While this therapy is initially effective, nearly all PCs become refractory to it. As hormone receptors play a crucial role in this process, we constructed a tissue microarray consisting of PC samples from 107 hormone-naïve (HN) and 101 castration-resistant (CR) PC patients and analyzed the androgen receptor (AR) gene copy number and the protein expression profiles of AR, Serin210-phosphorylated AR (pAR210), estrogen receptor (ER)β, ERα and the proliferation marker Ki67. The amplification of the AR gene was virtually restricted to CR PC and was significantly associated with increased AR protein expression (P<0.0001) and higher tumor cell proliferation (P=0.001). Strong AR expression was observed in a subgroup of HN PC patients with an adverse prognosis. In contrast, the absence of AR expression in CR PC was significantly associated with a poor overall survival. While pAR210 was predominantly found in CR PC patients (P<0.0001), pAR210 positivity was observed in a subgroup of HN PC patients with a poor survival (P<0.05). Epithelial ERα expression was restricted to CR PC cells (9%). ERβ protein expression was found in 38% of both HN and CR PCs, but was elevated in matched CR PC specimens. Similar to pAR210, the presence of ERβ in HN patients was significantly associated with an adverse prognosis (P<0.005). Our results strongly suggest a major role for pAR210 and ERβ in HN PC. The expression of these markers might be directly involved in CR tumor growth.

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer

2017 ◽  
Vol 99 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Filip Poelaert ◽  
Candy Kumps ◽  
Nicolaas Lumen ◽  
Stephanie Verschuere ◽  
Louis Libbrecht ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Copy Number ◽  
Receptor Gene ◽  
Gene Copy Number ◽  
Androgen Receptor Gene ◽  
Gene Copy ◽  
Treatment Naïve

Measurement science of the androgen receptor splice variant-7 protein in primary and castration-resistant prostate cancer tissue.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 151-151
Author(s):  
Adam Sharp ◽  
Ilsa Coleman ◽  
Jon Welti ◽  
Maryou B. Lambros ◽  
Wei Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Splice Variant ◽  
Response To Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Blood Samples ◽  
Castration Resistant ◽  
Measurement Science ◽  
Androgen Receptor Splice Variant

151 Background: Liquid biopsies demonstrate the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced benefit from endocrine therapies in castration resistant prostate cancer (CRPC). These studies provide little information pertaining to AR-V7 expression in PC tissue. Methods: AR-V7 protein expression was determined for 358 primary PC samples and 293 metastatic CRPC biopsies by immunohistochemistry. Associations with disease progression, full length AR (AR-FL) expression, response to therapy, gene expression, and circulating tumor cell (CTC) AR-V7 status were investigated. Results: AR-V7 protein is rarely expressed ( < 1% of 358 cases) in primary PC but is frequently detected (75% of 40 cases) following primary androgen deprivation therapy (ADT) alone (H-score 40; interquartile range 1.25-92.5), with a further significant (p = 0.020) increase following abiraterone or enzalutamide therapy (90; 20-150). In CRPC, AR-V7 expression is mainly nuclear (94% of 144 cases), correlates with AR-FL expression (p = < 0.001), and is homogeneous within single metastases (p = 0.997) but heterogeneous in different metastases from the same patient (p < 0.001). In addition, AR-V7 expression correlates with a 59-gene signature, including HOXB13, a co-regulator of AR-V7 function. Moreover, AR-V7 negative disease associates with better PSA response (p = 0.03) and overall survival (p = 0.02) from endocrine therapies. Finally, CTC+/AR-V7+ blood samples had significantly (p = 0.004) higher AR-V7 protein expression (100; 62.5-147.5) in paired tissue biopsy compared to CTC+/AR-V7- blood samples (15; 0.0-112.5), and AR-V7 protein expression is frequently detected (63% of 16 samples) in tissue of patients with CTC- blood samples. Conclusions: AR-V7 protein is not expressed until castration resistance and occurs after primary ADT alone. Levels of AR-V7 protein vary between metastases, and although AR-V7 associates with response to endocrine therapies, this suggests multiple resistance mechanisms exist in the same patient. If developed, agents targeting AR-V7 may be best explored earlier in the course of disease and in combination with other therapies.

Combination Therapies Using Metformin and/or Valproic Acid in Prostate Cancer: Possible Mechanistic Interactions

2019 ◽  
Vol 19 (5) ◽  
pp. 368-381 ◽  
Author(s):  
Linh N.K. Tran ◽  
Ganessan Kichenadasse ◽  
Pamela J. Sykes
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Androgen Receptor ◽  
Gene Fusion ◽  
Combination Therapies ◽  
Slowing Down ◽  
Castration Resistant ◽  
Local Pca ◽  
End Stage ◽  
Fusion Products

Prostate cancer (PCa) is the most frequent cancer in men. The evolution from local PCa to castration-resistant PCa, an end-stage of disease, is often associated with changes in genes such as p53, androgen receptor, PTEN, and ETS gene fusion products. Evidence is accumulating that repurposing of metformin (MET) and valproic acid (VPA) either when used alone, or in combination, with another therapy, could potentially play a role in slowing down PCa progression. This review provides an overview of the application of MET and VPA, both alone and in combination with other drugs for PCa treatment, correlates the responses to these drugs with common molecular changes in PCa, and then describes the potential for combined MET and VPA as a systemic therapy for prostate cancer, based on potential interacting mechanisms.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide

2017 ◽  
Vol 28 (9) ◽  
pp. 2264-2271 ◽  
Author(s):  
D.E. Rathkopf ◽  
M.R. Smith ◽  
C.J. Ryan ◽  
W.R. Berry ◽  
N.D. Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Immune checkpoint B7‐H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer

The Prostate ◽  
2021 ◽  
Author(s):  
Caroline E. Nunes‐Xavier ◽  
Wanja Kildal ◽  
Andreas Kleppe ◽  
Håvard E. Danielsen ◽  
Håkon Wæhre ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Protein Expression ◽  
Immune Checkpoint ◽  
Receptor Status ◽  
Poor Outcome
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