Androgen receptor gene mutations in human prostate cancer.

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作者：

Newmark JR; Hardy DO; Tonb DC; Carter BS; Epstein JI; Isaacs WB; Brown TR; Barrack ER

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摘要：

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.

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关键词：

Humans Adenocarcinoma Prostatic Neoplasms Threonine DNA Primers DNA, Neoplasm DNA-Binding Proteins Receptors, Androgen Polymerase Chain Reaction Base Sequence