Identification of differentially expressed genes in prostatic epithelium in relation to androgen receptor CAG repeat length.
The CAG repeat within exon 1 of the androgen receptor (AR) has been associated with the development of prostate cancer. The shorter number of glutamine residues in the protein has been associated with a higher transcriptional activity of the AR and increased relative risk for prostate cancer. In an attempt to identify differentially expressed genes in prostate cancer in relation to AR CAG repeat length variation, in this study we used total mRNA from normal and tumor tissues from 2 prostate cancer patients with AR alleles containing 19 and 26 CAG repeats to perform differential-display RT-PCR analysis. We were able to identify 48 different transcripts that showed homology to several known genes associated with different biological pathways. Among the differentially expressed genes, ATRX and SFRP1 were further validated by quantitative RT-PCR. The transcripts of both ATRX and SFRP1 genes proved to be down-regulated in most of the prostate tumors analyzed by quantitative RT-PCR. Hypermethylation of the promoter region of the SFRP1 gene was found in 17.5% (7/40) of the cases analyzed and was associated with the loss of SFRP1 expression (p=0.014). The differentially expressed genes identified in this study are implicated in several cellular pathways that, when up- or down-regulated, might play a role in the tumorigenic process of the prostate.
Coutinho-Camillo
C M
CM
Laboratório de Genética Molecular do Câncer, Disciplina de Oncologia, Departamento de Radiologia, FMUSP, São Paulo, Brazil.
Miracca
E C
EC
dos Santos
M L
ML
Salaorni
S
S
Sarkis
A S
AS
Nagai
M A
MA
D000368:Aged; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction
C410798:AR protein, human; D017931:DNA Primers; D011944:Receptors, Androgen