Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene

Sleddens, Hein F.B.M.; Oostra, Ben A.; Brinkmann, A.O.; Trapman, Jan

doi:10.1093/hmg/2.4.493

Cited by 85 publications

(76 citation statements)

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“…Sense and antisense primers were 5'-TGCGCGAAGTGATCCAGAAC-3' and 5'-CTTGGGGAGAAC-CATCCTCA-3' respectively. These primers flank a trinucleotide repeat polymorphism in exon 1 of the androgen receptor gene (Sleddens et al, 1992) as well as two HpaII restriction endonuclease sites located within 100 bases of this polymorphism (Allen et al, 1992 [a-32P]dCTP (ICN Radiochemicals, Irvine, CA, USA). Primers for this reamplification reaction were: 5'-GAAGATTCAGC-CAAGCTCAA-3' and 5'-TGAAGGTTGCTGTTCCTCAT-3'.…”

Section: Analysis Of X-chromosome Inactivationmentioning

confidence: 99%

“…This enzyme is methylation sensitive and therefore does not cleave DNA at methylated sites. The digested fragments were amplified enzymatically using primers flanking a trinucleotide repeat polymorphism in the androgen receptor gene on chromosome Xq (Sleddens et al, 1992). These primers also flanked two sites for the HpaII restriction endonuclease that are adjacent to the trinucleotide repeat.…”

Section: Methylation Of the Myodl Locus In Ovarian Cystadenomas Lmp mentioning

confidence: 99%

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Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Cheng

Schmütte²,

Cofer³

et al. 1997

Br J Cancer

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Summary We compared global levels of DNA methylation as well as methylation of a specific locus (MyoDl) in ovarian cystadenomas, ovarian tumours of low malignant potential (LMP) and ovarian carcinomas to investigate the association between changes in DNA methylation and ovarian tumour development. As we realized that cystadenomas showed different methylation patterns from both LMP tumours and carcinomas, we verified their monoclonal origin as a means of confirming their true neoplastic nature. High-pressure liquid chromatographic (HPLC) analyses showed that global methylation levels in LMP tumours and carcinomas were 21% and 25% lower than in cystadenomas respectively (P = 0.0001 by one-way variance analysis). Changes in the methylation status of the MyoDl locus were not seen in any of ten cystadenomas analysed but were present in five of ten LMP tumours and in five of ten carcinomas (P = 0.03). These findings suggest that alterations in DNA methylation are absent (or at least not as extensive) in ovarian cystadenomas, but are present in LMP tumours, the phenotypic features of which are intermediate between those of benign and malignant ovarian tumours. The results also emphasize the merit of distinguishing ovarian LMP tumours from cystadenomas, in spite of their similar clinical characteristics.

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Section: Analysis Of X-chromosome Inactivationmentioning

confidence: 99%

Section: Methylation Of the Myodl Locus In Ovarian Cystadenomas Lmp mentioning

confidence: 99%

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Cheng

Schmütte²,

Cofer³

et al. 1997

Br J Cancer

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“…There is only one AR gene located at Xq11-12 12 , but there are multiple allelic variants of the AR gene in the general population 13 due to two polymorphic trinucleotide repeats of CAG and GGN, coding for glutamine and glycine, respectively. Each polymorphism is varying in length among individuals in the general population and both the CAG and the GGN repeats have been found to regulate AR activity in vitro 14,15 .…”

Section: Introductionmentioning

confidence: 99%

The 5α-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population

et al. 2005

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ObjectivesTo compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5α-reductase II (SRD5A2) gene. Materials and MethodsThe SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n=89), benign prostate hyperplasia (n=45) and healthy military conscripts (n=223). ResultsThe SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p=0.026 and p=0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN<23 had a higher risk of dying from the disease than their counterparts with longer repeats. ConclusionsMen with CaP were more often genetically predisposed to a higher enzymatic activity in the turn over from T to DHT compared to the general population. In our population, androgen receptor genotype affected CaP outcome.4

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“…27,28 The latter antisense oligonucleotides proved to be highly effective in suppression of AR expression and inhibition of the growth of LNCaP and LNCaP-abl cells.…”

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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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Trinucleotide (GGN) repeat polymorphism in the human androgen receptor (AR) gene

Cited by 85 publications

References 0 publications

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

The 5α-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population

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

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