scholarly journals Identification of Differentially Expressed Genes in Prostatic Epithelium in Relation to Androgen Receptor CAG Repeat Length

2006 ◽  
Vol 21 (2) ◽  
pp. 96-105 ◽  
Author(s):  
C.M. Coutinho-Camillo ◽  
E.C. Miracca ◽  
M.L. Dos Santos ◽  
S. Salaorni ◽  
A.S. Sarkis ◽  
...  

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.

2012 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
S Madjunkova ◽  
A Eftimov ◽  
V Georgiev ◽  
D Petrovski ◽  
A Dimovski ◽  
...  

Cag Repeat Number in the Androgen Receptor Gene and Prostate CancerProstate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ±2.65, in controls 22.28 ±2.86 (p = 0.009) and in BPH patients 22.1 ±2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.


2006 ◽  
Vol 21 (2) ◽  
pp. 96-105 ◽  
Author(s):  
C.M. Coutinho-Camillo ◽  
E.C. Miracca ◽  
M.L. dos Santos ◽  
S. Salaorni ◽  
A.S. Sarkis ◽  
...  

2008 ◽  
Vol 111 (1-2) ◽  
pp. 138-146 ◽  
Author(s):  
Jason Southwell ◽  
Shafinaz F. Chowdhury ◽  
Bruce Gottlieb ◽  
Lenore K. Beitel ◽  
Rose Lumbroso ◽  
...  

Author(s):  
Shiva Sharestani ◽  
Seyed Mehdi Kalantar ◽  
Nasrin Ghasemi ◽  
Ehsan Farashahi Yazd

Background: Androgens play a role in the development of male phenotype and spermatogenesis during puberty, the function of which is regulated by the androgen receptor (AR) gene. There is a polymorphism site in exon 1 of the gene encoding this receptor that can have different frequencies of CAG trinucleotide repeats and leads to the formation of polyglutamine chains of different lengths in the N-terminal domain of the AR protein and reduced sperm production by affecting spermatogenesis. Objective: To investigate whether the cause of a group of unexplained infertilities could be the increased frequency of CAG repeats in the AR gene of patients with oligozoospermia and azoospermia. Materials and Methods: In this case-control study, 84 men including 42 with unexplained infertility As a case group and 42 fertile men as a control group were selected. The frequency of CAG repeats was determined by the polymerase chain reaction method and then the difference in the frequency of these repeats was determined based on the difference in band size on the agarose gel. Results: The mean CAG repeat length in the azoospermia and oligozoospermia group was 17.5 ± 0.63 and in the fertile group it was 16.11 ± 0.75 (p = 0.46). In addition, most men (88.1% in the case group and 71.41% in the control group) had 13-23 repeats. Conclusion: No significant correlation was found between CAG repeat length and the risk of male factor infertility in an ethnically defined population of Iranian men. The role of regulatory factors and epigenetic changes should be taken into account too. Key words: Infertility, Azoospermia, Androgens, X chromosome, Spermatogenesis.


2011 ◽  
Vol 120 (02) ◽  
pp. 73-79 ◽  
Author(s):  
A. Schüring ◽  
A. Welp ◽  
J. Gromoll ◽  
M. Zitzmann ◽  
B. Sonntag ◽  
...  

AbstractPolycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS.In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay.Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002).The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome’s phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.


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