Loss of the Restriction Integrity of Ligand Binding Domain of the Androgen Receptor Gene May Predict Prostate Cancer

Background: Human Androgen Receptor (AR) functions as a steroid-hormone activator transcription factor. AR binds to its ligand (testosterone or dihyrotestosteron), translocated to the nucleus to stimulate the transcription of androgen responsive genes. Mutations in the Ligand Binding Domain (LBD) impair the receptor activity and play a crucial role in the development and progression of prostate cancer. Material and Methods: This work was designated to investigate the restriction integrity of the LBD and its association with benign prostatic hyperplasia (BPH) and Prostate Cancer (PCa). Exons of this domain (exons: 4-8) were amplified from prostate tissue of BPH and PCa patients and the restriction polymorphism was investigated in both BPH and PCa patients by SmlI, HphI and Tsp45I restriction enzymes in both BPH and PCa. Results: The data revealed the integrity exons 4-6 in both BPH and PCa patients. Exons 7 and 8, however have kept their constitutional pattern only in BPH patients. Hph1 site showed abnormal restriction pattern in 40% and 26.7% of PCa patients. Also, Tsp45I demonstrated restriction polymor-phism in 20% and 13% in PCa patients. Conclusion: Our data indicate that the loss of the restriction integrity in the C-terminal part (exons: 7 and 8) of the LBD is associated with the progression of benign prostatic hyper-plasia to prostate cancer.