Journal of Andrology
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Published-Ahead-of-Print October 3, 2007, DOI:10.2164/jandrol.107.003608

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Downregulation of Thymosin beta 4 Expression by Androgen in Prostate Cancer LNCaP Cells

Kazuhiro Iguchi , Mai Ito , Shigeyuki Usui , Atsushi Mizokami , Mikio Namiki , and Kazuyuki Hirano *

* To whom correspondence should be addressed. E-mail: hirano{at}gifu-pu.ac.jp.

BACKGROUND. Androgen-ablation therapy is an effective treatment for advanced prostate cancer, but the tumor often progresses toward a more aggressive phenotype. We determined the changes in genes associated with the malignant progression, and found increased thymosin beta4, involved in tumor metastasis, in androgen-sensitive LNCaP cells grown in the medium with androgen-deficient charcoal-stripped FCS. METHODS. The mRNA expression of thymosin beta4 was determined by real-time PCR analysis. The transcriptional activity of thymosin beta4 was measured by luciferase assay using reporter plasmid containing 5'-flanking region of thymosin beta4. RESULTS. Thymosin beta4 mRNA expression was increased in LNCaP cells in the androgen-deficient condition and decreased by dihydrotestosterone treatment. Androgen receptor antagonist bicalutamide inhibited thymosin beta4 expression in a dose-dependent manner. In androgen receptor-negative PC-3 cells, no significant effects on thymosin beta4 gene expression were observed. The regulation of thymosin beta4 mRNA expression by androgen is due to the transcriptional activation. Deletion analysis revealed that the region between -83 bp and -46 bp of thymosin beta4 gene is responsible for the regulation of the transcriptional activity by androgen. CONCLUSIONS. Thymosin beta4 expression is negatively controlled at the transcriptional level by androgen.


Key words: Androgen • Hormone • Prostate






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