Androgen receptor gene mutations in human prostate cancer.
To investigate the structural abnormality of the androgen receptor (AR) in human prostate cancers, exons B-H encoding DNA- and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products using originally designed oligoprimers. Tissues from 7 cases of untreated stage B prostate cancer surgically removed and from 8 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Two different mutations were identified in exons D and H in the different cancer foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu to His) was detected in the prostate, and the other in exon H (at codon 877, Thr to Ala) was found in metastatic tissues. In untreated cancer tissues and the other autopsy samples, no mutations were detected. The mutation in exon H was identical to that reported in LNCaP cells. These results indicate that AR gene mutations occur in relation to endocrine therapy-resistance, although the mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.
Suzuki
H
H
Department of Urology, School of Medicine, Chiba University, Japan.
Sato
N
N
Watabe
Y
Y
Masai
M
M
Seino
S
S
Shimazaki
J
J
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000409:Alanine; D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D014644:Genetic Variation; D006639:Histidine; D006801:Humans; D007930:Leucine; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics*; D013912:Threonine
D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen; D013912:Threonine; D006639:Histidine; D007930:Leucine; D000409:Alanine