Relative activity and specificity of promoters from prostate-expressed genes

Brookes, D.E.; Zandvliet, Dorothea W.J.; Watt, Fujiko; Russell, Pamela J.; Molloy, Peter L.

doi:10.1002/(sici)1097-0045(19980401)35:1<18::aid-pros3>3.0.co;2-d

Cited by 52 publications

(33 citation statements)

References 40 publications

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“…We studied AR transcriptional activity in a number of cell lines (prostatic and non-prostatic), utilising an androgen responsive reporter construct containing rat probasin promoter (Kasper et al 1994). This promoter sequence has previously been shown to be relatively androgen (Rennie et al 1993, Claessens et al 1996 and prostate specific (Greenberg et al 1994, Brookes et al 1998.…”

Section: Introductionmentioning

confidence: 95%

“…The actions of steroid hormone receptors and hormone responsive promoters in androgen responsive genes show both tissue and cellular specificity (Rennie et al 1993, Cleutjens et al 1996, Brookes et al 1998. To examine the effect of the AR CAG repeat polymorphism in vitro in relation to the pathogenesis of androgen-dependent diseases within the prostate we have characterised the transcriptional activity of the AR with variable numbers of CAG repeats within the normal range.…”

Section: Introductionmentioning

confidence: 99%

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Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines

Beilin¹,

Ball²,

Favaloro³

et al. 2000

Journal of Molecular Endocrinology

233

146

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The action of androgens is essential for the development of benign prostatic hyperplasia and carcinoma of the prostate. The androgen receptor is a ligand-dependent nuclear transcription factor. The transcriptional activation domain of the androgen receptor gene contains a polymorphic CAG repeat sequence. A shorter CAG repeat sequence within the normal range has been reported to be associated with increased risk of prostate cancer and symptomatic benign prostatic hyperplasia. Here, we examine the in vitro transcriptional activity of the androgen receptor (AR) with different numbers of CAG repeats within the normal range in a number of different cell lines of prostatic (LNCaP, PC3) and non-prostatic (COS-1, MCF7) origin. We utilize a luciferase reporter driven by the rat probasin promoter ( 286/+28) containing two androgen receptor binding sites. Transcriptional activation of the androgen responsive reporter was observed to be greater with the AR containing 15 vs 31 CAG repeats in COS-1 cells (123·2 16·6 vs 78·2 10·9, P value 0·01) and the well differentiated prostate cancer cell line LNCaP (103·4 17·7 vs 81·4 7·7, P value 0·045). No difference was observed in the poorly differentiated prostate cancer cell line, PC3 (106·9 21·9 vs 109·6 21·4, P value >0·5) or the breast cancer cell line MCF7 (120·4 39·4 vs 103·1 23·1, P value >0·5). Dose-response experiments with varying quantities of ligand (0·01, 0·1, 1 and 10 nM dihydrotestosterone) or AR cDNA did not demonstrate significant differences in transactivation of the androgen responsive reporter in PC3 cells by the different AR constructs. This suggests that the lack of influence of CAG number in this prostatic cell line is not related to dose of ligand or quantity of androgen receptor. Western immunoblot analysis of androgen receptor protein in transiently transfected COS-1 cells did not demonstrate a difference in the expression of the androgen receptor protein with different numbers of CAG repeats following incubation in the presence or absence of androgen. Gel shift assay did not demonstrate increased DNA binding by androgen receptor with a shorter CAG repeat sequence. These experiments using a relatively androgen-and prostate-specific reporter provide evidence for an inverse relationship between androgen receptor transcriptional activity and the number of CAG repeats in the transcriptional activation domain. The effect of CAG repeat number was cell specific suggesting the involvement of accessory factors expressed differentially between different cell lines.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines

Beilin¹,

Ball²,

Favaloro³

et al. 2000

Journal of Molecular Endocrinology

233

146

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show abstract

“…For this purpose, tissue-or tumor-specific promoters have been proposed to control the expression of transgene or essential viral gene(s). 4,7,8 However, an influence of infected cell proteins (ICPs), encoded by the viral genes, on the expression of transgene was recently noticed. 9 HSV viral proteins are divided into three major kinetic classes on the basis of requirements for their expression and the times of their maximum rates of synthesis: immediate early (IE), early and late.…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Yang

Song

et al. 2003

Gene Ther

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“…12,13 Such therapies can be further refined by the use of prostate-specific promoters to drive gene expression. 7,[14][15][16][17][18][19] For systemic therapy, replication competent adenoviruses that are controlled by a tissue-specific promoter are under development. 20 Alternatively, tumor targeting can be achieved by altering the normal tropism of adenovirus infection.…”

Section: Introductionmentioning

confidence: 99%

Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models

et al. 2002

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Relative activity and specificity of promoters from prostate-expressed genes

Cited by 52 publications

References 40 publications

Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines

Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines

Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models

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