title: In vivo amplification of the androgen receptor gene and progression of human prostate cancer.
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.
authors.affiliation: Laboratory of Cancer Genetics, Tampere University Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Visakorpi
authors.forename: E
authors.initials: E
authors.lastname: Hyytinen
authors.forename: P
authors.initials: P
authors.lastname: Koivisto
authors.forename: M
authors.initials: M
authors.lastname: Tanner
authors.forename: R
authors.initials: R
authors.lastname: Keinänen
authors.forename: C
authors.initials: C
authors.lastname: Palmberg
authors.forename: A
authors.initials: A
authors.lastname: Palotie
authors.forename: T
authors.initials: T
authors.lastname: Tammela
authors.forename: J
authors.initials: J
authors.lastname: Isola
authors.forename: O P
authors.initials: OP
authors.lastname: Kallioniemi
mesh_terms: D000368:Aged; D004351:Drug Resistance / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D011944:Receptors, Androgen / Q000235:genetics*; D014960:X Chromosome
chemical_list: D011944:Receptors, Androgen