Partial association of restriction polymorphism of the ligand binding domain of human androgen receptor in prostate cancer

Abstract

Background: Human androgen receptor (AR) functions as a steroid-hormone activated transcription factor. The receptor binds to its ligand (testosterone or dihydrotestosterone) and is 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 (PCa).

Materials 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. Exons of this domain (exons: 4–8) were amplified from prostate tissue of BPH and PCa patients and the restriction polymorphism was investigated by SmlI, HphI and Tsp45I restriction enzymes in both BPH and PCa groups.

Results: Data revealed the integrity of 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 an abnormal restriction pattern in 40% and 26.7% of PCa patients. Also, Tsp45I demonstrated restriction polymorphism in 20% and 13% of PCa patients.

Conclusion: Our results 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 hyperplasia to prostate cancer.

Keywords:  Androgen receptor; Ligand binding domain; Prostate cancer; Benign prostatic hyperplasia; Polymorphism