Downregulation of thymosin β4 expression by androgen in prostate cancer LNCaP cells

Androgen ablation therapy is an effective treatment for advanced prostate cancer, but the tumor; of, ten. progresses toward a more aggressive phenotype. We determined the changes in genes associated with the malignant progression and found increased thymosin beta 4, involved in tumor metastasis, in androgen-sensitive LNCaP cells grown in the medium with androgen-deficient, charcoal-stripped fetal calf serum. The mRNA expression of thymosin beta 4 was determined by real-time polymerase chain reaction analysis. The transcriptional activity of thymosin beta 4 was measured by luciferase assay using reporter plasmid containing 5'-flanking region of thymosin beta 4. Thymosin beta 4 mRNA expression was increased in LNCaP cells in the androgen-deficient condition and decreased by dihydrotestosterone treatment. Androgen receptor antagonist bicalutamide inhibited thymosin beta 4 expression in a dose-dependent manner. In androgen receptor-negative PC-3 cells, no significant effects on thymosin beta 4 gene expression were observed. The regulation of thymosin beta 4 mRNA expression by androgen, is due, to the transcriptional activation. Deletion analysis' revealed that the region between -83 bp and -416 bp of the thymosin beta 4 gene is responsible for the I regulation of the transcriptional activity by androgen. Thymosin beta 4 expression is negatively controlled at the transcriptional level by androgen.