Amplification of the androgen receptor gene in bone metastases from hormone‐refractory prostate cancer

Brown, Richard S.; Edwards, Joanne; Doğan, Ahmet; Payne, Heather; Harland, S. J.; Bartlett, John M.S.; Masters, J. R. W.

doi:10.1002/path.1206

Cited by 82 publications

(51 citation statements)

References 19 publications

(61 reference statements)

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“…It was also demonstrated that AR protein expression was 60% higher in tumors with an AR copy number >2.1. Additionally, the study found that X-chromosome copy number was increased in up to 13.8% of cancer specimens, which corresponds with the fact that AR copy number can be increased by X-chromosome polysomy, but will not impact on AR protein expression (5,15,21).…”

Section: Discussionmentioning

confidence: 97%

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis

et al. 2015

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Abstract. Prostate cancer (PCa) is the most frequently diagnosed non-skin cancer and the second highest cause of cancer-related mortality in adult males worldwide. PCa is highly dependent upon androgen receptor (AR) signaling for cell proliferation and survival. The AR therefore plays a vital role in the develop ment and function of normal and malignant prostate cells or PCa recurrence. The present study aimed to examine the ubiquity of AR amplification in PCa recurrence, even in the absence of androgen. For this purpose, specimens were collected from 37 patients. The amplification of AR and the number of X chromosomes were determined by two-colored fluorescence in situ hybridization analysis. The automated image analysis was used to determine the protein expression of AR. Clinical characteristics and survival in patients whose tumors showed or did not show AR amplification and in X-chromosome polysomy with PCa recurrence has also been compared. The results showed that >35% of patients (13 specimens) exhibited AR amplification. It was also observed that AR was immunostained more intensely in the tumors with amplified AR compared with those tumors with non-amplified AR. This study demonstrated an influential role of AR in tumor growth and progression even after the deprivation of androgen, as well as showing the potential contribution of AR amplification to AR activation even in the relative absence of androgen.

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Section: Discussionmentioning

confidence: 97%

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis

et al. 2015

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“…According to our data, AR signalling is sustained in c-myc-expressing cells. In the literature, numerous reports have shown that c-myc (10,12) or AR (36,37) can be amplified, and at least one report has shown that both genes can be coamplified in AIPC (38). Inactivation of AR in prostate cancer has been reported in rare cases (39).…”

Section: Discussionmentioning

confidence: 99%

Myc confers androgen-independent prostate cancer cell growth

Bernard¹,

Pourtier-Manzanedo²,

Gil³

et al. 2003

J. Clin. Invest.

123

129

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“…Gene amplification, which may occur due to an increase in copy number of certain regions of chromosomes, has been identified in several malignancies, including PCa (18,19). Previous studies have reported that the genetic duplication of various genes was associated with PCa malignancy, including androgen receptor (20), enhancer of zeste homolog 2 (21), eukaryotic translation initiation factor 3 (22), calcium-activated potassium channel subunit α-1 (23), minichromosome maintenance complex component 7 (24), prostate leucine zipper (25) and hypoxia-inducible factor 1 (26).…”

Section: Her2 Gene Amplification In Patients With Prostate Cancermentioning

confidence: 99%

HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

et al. 2016

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Abstract. Prostate cancer (PCa) is one of the most widespread malignancies in the world. The role of the human epidermal growth factor receptor 2 (HER2) in the pathogenesis and progression of human PCa remains poorly understood. In contradiction with breast cancer, studies on HER2 overexpression and gene amplification in PCa have produced varying results, although the HER2 oncogene has been implicated in the biology of numerous tumor types, and serves as a prognostic marker and therapeutic target in breast cancer. Technical challenges are considered the main reasons for data discrepancies. Amplification of the HER2 gene has previously been reported in PCa, in which it was associated with tumor progression. The present study aimed to evaluate the prevalence and clinical significance of HER2 amplification in PCa. A total of 32 biopsy samples obtained from human prostate adenocarcinomas were evaluated by chromogenic in situ hybridization (CISH) to determine the frequency of patients with HER2 gene amplifications. High copy numbers of HER2 were detected in 19 of the prostate tumors analyzed. The results of the present study suggested that, in patients without amplification of HER2, high levels of prostate-specific antigen or a high Gleason score were not significantly correlated with a high pathologic stage. Furthermore, amplification levels of the HER2 gene were directly associated with pathologic stage in patients with PCa. Therefore, the potential use of HER2 as a prognostic factor or therapeutic target for PCa warrants further study. IntroductionProstate cancer (PCa), a common non-skin, sex-limited cancer, is the second cause of cancer-associated mortality (after lung cancer) in the USA (1,2) and the second most prevalent cancer among Iranian men (3). Worldwide, PCa is the second most commonly diagnosed cancer and, according to the International Agency for Research on Cancer's GLOBOCAN 2012 (4) database, it is the fifth leading cause of cancer-associated mortality in men. The incidence of PCa is increasing worldwide, although there is a marked variation in its incidence among different regions (5). The clinical configuration of PCa has noticeably altered over the past few years. As a localized disease, it is easily treated by radical radiation therapy or a prostatectomy; however, if the tumor becomes malignant, it transforms into a life-threatening disease (6).The progression and application of novel high-resolution technologies has enhanced the detection of genomic alterations, enabling elucidation of the complex nature and heterogeneity of PCa (7). The differentiation of PCa tumors is typically based on the serum expression levels of prostate-specific antigen (PSA), although, in certain cases, PSA levels do not accurately reflect tumor burden (8). Previous studies have identified a number of genetic, epigenetic and environmental risk factors for PCa (9-11). Among them, genetic aberrations and chromosomal changes have been suggested to serve a significant role in the development and progression of PCa (12)

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Amplification of the androgen receptor gene in bone metastases from hormone‐refractory prostate cancer

Cited by 82 publications

References 19 publications

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis

Myc confers androgen-independent prostate cancer cell growth

HER2 gene amplification in patients with prostate cancer: Evaluating a CISH-based method

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