IN-VIVO AMPLIFICATION OF THE ANDROGEN RECEPTOR GENE AND PROGRESSION OF HUMAN PROSTATE-CANCER

Overexpression of amplified genes is often associated with the acquisi tion of resistance to cancer therapeutic agents in vitro. We have iden tified a similar molecular mechanism in vivo for endocrine treatment f ailure in human prostate cancer which involves amplification of the an drogen receptor (AR) gene. Comparative genomic hybridization shows tha t amplification of the Xq11-q13 region (the location), is common in tu mours recurring during androgen deprivation therapy. We found high-lev el AR amplification in seven of 23 (30%) recurrent tumours, but in non e of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivat ion therapy by facilitating tumour cell growth in low androgen concent rations.