Additional activation of the AR gene may be involved in the development of the castration resistance phenotype in prostate cancer

Abstract

Introduction: Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR.

Materials and methods: To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays.

Results: In the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR.

Conclusion: Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype.

Keywords: Androgen receptor; Cromosoma X; HUMARA; LNCaP; PC-3; Receptor de andrógenos; X chromosome.