In vivo amplification of the androgen receptor gene and progression of human prostate cancer

T Visakorpi, E Hyytinen, P Koivisto, M Tanner… - Nature …, 1995 - nature.com
T Visakorpi, E Hyytinen, P Koivisto, M Tanner, R Keinänen, C Palmberg, A Palotie
Nature genetics, 1995nature.com
Overexpression of amplified genes is often associated with the acquisition of resistance to
cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo
for endocrine treatment failure in human prostate cancer which involves amplification of the
androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification
of the Xq11–q13 region (the location), is common in tumours recurring during androgen
deprivation therapy. We found high–level AR amplification in seven of 23 (30%) recurrent …
Abstract
Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11–q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high–level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations.
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