Dual androgen-response elements mediate androgen regulation of MMP-2 expression in prostate cancer cells / 亚洲男科学杂志(英文版)
Asian Journal of Andrology
;
(6): 41-50, 2007.
Article
Dans Anglais
| WPRIM
| ID: wpr-253782
ABSTRACT
<p><b>AIM</b>To characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression.</p><p><b>METHODS</b>MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays (EMSA) were used to verify the identified AREs in the MMP-2 promoter.</p><p><b>RESULTS</b>Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 (relative to the start codon) of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5'-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor (AR) interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay.</p><p><b>CONCLUSION</b>Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.</p>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Tumeurs de la prostate
/
ARN messager
/
Chromatine
/
Régulation de l'expression des gènes codant pour des enzymes
/
Régulation de l'expression des gènes tumoraux
/
Mutagenèse dirigée
/
Régions promotrices (génétique)
/
Délétion de séquence
/
Gènes rapporteurs
Limites du sujet:
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Asian Journal of Andrology
Année:
2007
Type:
Article
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