Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene

Abstract

The human androgen receptor (AR) gene promoter lies in a GC-rich region containing two principal sites of transcription initiation and a putative Sp1 protein-binding site, without typical "TATA" and "CAAT" boxes. It has been suggested that mutations within the 5'untranslated region (5'UTR) may contribute to the development of prostate cancer by changing the rates of gene transcription and/or translation. In order to investigate this question, the aim of the present study was to search for the presence of mutations or polymorphisms at the AR-5'UTR in 92 prostate cancer patients, where histological diagnosis of adenocarcinoma was established in specimens obtained from transurethral resection or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA samples of the patients and of 100 healthy male blood donors, included as controls. Conformation-sensitive gel electrophoresis was used for DNA sequence alteration screening. Only one band shift was detected in one individual from the blood donor group. Sequencing revealed a new single nucleotide deletion (T) in the most conserved portion of the promoter region at position +36 downstream from the transcription initiation site I. Although the effect of this specific mutation remains unknown, its rarity reveals the high degree of sequence conservation of the human androgen promoter region. Moreover, the absence of detectable variation within the critical 5'UTR in prostate cancer patients indicates a low probability of its involvement in prostate cancer etiology.

Mutation screening of the androgen receptor promoter and untranslated regions in prostate cancer

“…The third alteration ,which was found in the one healthy man out of 100 blood donors, was 25delT in a conserved region of 5 0 -UTR. In the same study no germ-line alterations were found among 92 prostate cancer patients [25]. In addition, one somatic change in 3 0 -UTR of a prostate cancer specimen has been reported [26].…”

“…Two single cases of germ-line alterations have been identified in the 5 0 -UTR and one in the promoter region, two of these in prostate cancer patients [24], and one in a healthy male blood donor [25]. The alterations that were found in one prostate cancer patient were G-10T within the ARTIS I and C203A within a GC rich region of the 5 0 -UTR [24].…”