PMID- 10629558
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20061115
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 189
IP  - 4
DP  - 1999 Dec
TI  - Androgen receptor gene mutations in hormone-refractory prostate cancer.
PG  - 559-63
AB  - Prostate cancer is considered to be one of the most hormone-dependent human
      malignancies. As a key mediator of hormonal response, the androgen receptor (AR) 
      is believed to have an important role in the progression of prostate cancer.
      Mutations in the coding region of the AR gene have been found in both untreated
      and hormone-refractory prostate cancer, but the frequency of such mutations at
      different stages of the disease is poorly documented and even contradictory
      results have been published. In the present study, the frequency of AR gene
      mutations was determined in 30 locally recurrent and two metastatic
      hormone-refractory prostate tumours using the polymerase chain reaction (PCR),
      non-radioactive single strand conformation polymorphism (SSCP), and sequencing.
      The length of the polymorphic CAG repeat, which is inversely correlated with the 
      ability of the AR to activate transcription, was also analysed as well as the GGC
      repeat. Twelve samples were known to contain an AR gene amplification.
      Altogether, one point mutation (Gly(674)-->Ala) and one microsatellite mutation
      (CAG(20)-->CAG(18)) were found, both in cancers containing the AR gene
      amplification. The mean lengths of the polymorphic CAG and GGC repeats were
      similar to those observed in the normal population. These results favour the view
      that mutations in the AR gene are rare in hormone-refractory prostate cancer and 
      do not play an important role, at least, in local relapse. Instead, the
      amplification and consequent overexpression of the wild-type AR gene seem to be
      the most common alteration involving the AR in hormone-refractory prostate
      cancer.
CI  - Copyright 1999 John Wiley & Sons, Ltd.
FAU - Wallen, M J
AU  - Wallen MJ
AD  - Laboratory of Cancer Genetics, Institute of Medical Technology, University of
      Tampere and Tampere University Hospital, FIN-33101 Tampere, Finland.
FAU - Linja, M
AU  - Linja M
FAU - Kaartinen, K
AU  - Kaartinen K
FAU - Schleutker, J
AU  - Schleutker J
FAU - Visakorpi, T
AU  - Visakorpi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Carcinoma/*genetics/pathology
MH  - *Gene Amplification
MH  - Humans
MH  - Male
MH  - Mutagenesis, Site-Directed
MH  - *Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Prostatic Neoplasms/*genetics/pathology
MH  - Receptors, Androgen/*genetics
MH  - Sequence Analysis, DNA
EDAT- 2000/01/12 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/12 09:00
PHST- 2000/01/12 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/12 09:00 [entrez]
AID - 10.1002/(SICI)1096-9896(199912)189:4<559::AID-PATH471>3.0.CO;2-Y [pii]
AID - 10.1002/(SICI)1096-9896(199912)189:4<559::AID-PATH471>3.0.CO;2-Y [doi]
PST - ppublish
SO  - J Pathol. 1999 Dec;189(4):559-63. doi:
      10.1002/(SICI)1096-9896(199912)189:4<559::AID-PATH471>3.0.CO;2-Y.