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Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter.

Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Research Abstract Details 

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  • Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Abstract Text:

    jason t readJason T Read,maziar rahmaniMaziar Rahmani,seti boroomandSeti Boroomand,sima allahverdianSima Allahverdian,bruce m mcmanusBruce M McManus,paul s renniePaul S Rennie,jason t readJason T Read,maziar rahmaniMaziar Rahmani,seti boroomandSeti Boroomand,sima allahverdianSima Allahverdian,bruce m mcmanusBruce M McManus,paul s renniePaul S Rennie,

    Versican, one of the key components of prostatic stroma, plays a central role in tumor initiation and progression. Here, we investigated promoter elements and mechanisms of androgen receptor (AR)-mediated regulation of the versican gene in prostate cancer cells. Using transient transfection assays in prostate cancer LNCaP and cervical cancer HeLa cells engineered to express the AR, we demonstrate that the synthetic androgen R1881 and dihydrotestosterone stimulate expression of a versican promoter-driven luciferase reporter vector (versican-Luc). Further, both basal and androgen-stimulated versican-Luc activities were significantly diminished in LNCaP cells, when AR gene expression was knocked down using a short hairpin RNA. Methylation-protection footprinting analysis revealed an AR-protected element between positions +75 and +102 of the proximal versican promoter, which strongly resembled a consensus steroid receptor element. Electrophoretic mobility shift and supershift assays revealed strong and specific binding of the recombinant AR DNA binding domain to oligonucleotides corresponding to this protected DNA sequence. Site-directed mutagenesis of the steroid receptor element site markedly diminished R1881-stimulated versican-Luc activity. In contrast to the response seen using LNCaP cells, R1881 did not significantly induce versican promoter activity and mRNA levels in AR-positive prostate stromal fibroblasts. Interestingly, overexpression of beta-catenin in the presence of androgen augmented versican promoter activity 10- and 30-fold and enhanced versican mRNA levels 2.8-fold in fibroblasts. In conclusion, we demonstrate that AR transactivates versican expression, which may augment tumor-stromal interactions and may contribute to prostate cancer progression.

    Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Publishing Authors By Initials

    jt readJT Read,m rahmaniM Rahmani,s boroomandS Boroomand,s allahverdianS Allahverdian,bm mcmanusBM McManus,ps renniePS Rennie,jt readJT Read,m rahmaniM Rahmani,s boroomandS Boroomand,s allahverdianS Allahverdian,bm mcmanusBM McManus,ps renniePS Rennie,

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    Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 31954-63

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 28

    MONTH: 08

    YEAR: 2007

    Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

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    Grant and Affiliation Information for Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter.

    AFFILIATION: Prostate Center, Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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