The androgen receptor gene mutations database

Gottlieb, Bruce; Lehväslaiho, Heikki; Beitel, Lenore K.; Lumbroso, Rose; Pinsky, Leonard; Trifiro, Mark

doi:10.1093/nar/24.1.151

Cited by 135 publications

(83 citation statements)

References 44 publications

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“…In prostate cancer, 17 different single base mutations with amino acid substitutions has been reported. 26 In this study, three silent mutations were detected in three cases, which suggested that AR gene mutation may not play an important role in the disease progression. A previous report showed silent base changes in the AR coding region, but that the significance of AR function was not clear.…”

Section: Discussionmentioning

confidence: 64%

Expression and somatic mutation on androgen receptor gene in prostate cancer

et al. 2002

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Background : Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers. Methods : Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations. Results : Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 ± 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 ± 18.3% in average) ( P < 0.001). A significant correlation was obtained between progressionfree survival and AR expression ( P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas. Conclusion : We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.

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Section: Discussionmentioning

confidence: 64%

Expression and somatic mutation on androgen receptor gene in prostate cancer

et al. 2002

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“…In contrast to the androgen receptor gene [43], belonging to the same receptor family, not a single TRβ gene mutation has been reported in non-coding regions or reported to produce abnormal splice variants. Sequencing of cDNA is important in subjects with clinically proven RTH in whom no mutations could be found in genomic DNA.…”

Section: Geneticsmentioning

confidence: 96%

Syndromes of Reduced Sensitivity to Thyroid Hormone

Weiss

Dumitrescu

Refetoff

2010

Genetic Diagnosis of Endocrine Disorders

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“…13,14 Another important fact is the occurrence of AR gene mutations that can result in a promiscuous receptor with a broad hormone binding and transactivation spectrum. 15,16 Activation of mutated AR has been shown for steroid hormones such as estrogens, progestins, adrenal androgens, and dihydrotestosterone metabolites, and even for the nonsteroidal anti-androgens flutamide and nilutamide. [17][18][19][20][21] Prostate tumor progression can also be accompanied by AR activation through growth factors and protein kinase A activators.…”

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confidence: 99%

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

et al. 2000

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Currently available methods for treatment of human prostatic carcinoma aim to inactivate the androgen receptor (AR) by androgen deprivation or blockade with anti-androgens. Failure of endocrine therapy and tumor progression is characterized by androgenindependent growth despite high levels of AR expression in metastatic disease. We inhibited AR expression in LNCaP prostate tumor cells by using antisense AR oligodeoxynucleotides (ODNs) and explored whether antisense AR treatment would be conceivable as a therapy for advanced prostate cancer. Among the various AR antisense ODNs tested, a 15-base ODN targeting the CAG repeats encoding the poly-glutamine region of the AR (as750/15) was found to be most effective. Treatment of LNCaP cells with as750/15 reduced AR expression to ϳ2% within 24 hours compared with mock-treated controls. AR down-regulation resulted in significant cell growth inhibition, strongly reduced secretion of the androgen-regulated prostate-specific antigen, reduction of epidermal growth factor receptor expression, and an increase in apoptotic cells. Mis-sense and mismatched control ODNs had no or only slight effects. Antisense inhibition was also very efficient in LNCaP-abl cells, a subline established after long-term androgen ablation of LNCaP cells, resulting in inhibition of AR expression and cell proliferation that was similar to that seen for parental LNCaP cells. This study shows that inhibition of AR expression by antisense AR ODNs may be a promising new approach for treatment of advanced human prostate cancer. Cancer Gene Therapy (2000) 7, 997-1007

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The androgen receptor gene mutations database

Cited by 135 publications

References 44 publications

Expression and somatic mutation on androgen receptor gene in prostate cancer

Expression and somatic mutation on androgen receptor gene in prostate cancer

Syndromes of Reduced Sensitivity to Thyroid Hormone

Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides

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