Androgen stimulation of PCA3 and miR-141 and their release from prostate cancer cells

Prostate cancer antigen 3 [PCA3] and microRNA-141 [miR-141] are emerging molecules in prostate cancer [PCa] pathogenesis and have been shown to be involved in androgen signaling. In this original research, we designed an experimental cell model with androgen-sensitive LNCaP cells to comparatively assess the extent of androgen responsiveness of PCA3-mRNA and miR-141 along with prostate specific antigen [PSA]- mRNA and their release into culture medium. These molecules were also measured in the plasma of the patients with early PCa which is considered to be analogous to androgenresponsive cells. In this experimental study, LNCaP cells were exposed to androgen ablation for 48 hours and treated then with dihydrotestosterone [DHT] for 24 hours. Expression of all three RNA molecules in cells, culture medium or plasma was measured by quantitative polymerase chain reaction [qPCR]. Our results show that DHT differentially affects the expression of these molecules. PCA3 was the most evidently induced molecule [up to 400-fold, p<0.001], while the effect was moderate for PSA-mRNA [up to 30-fold, p<0.001]. In contrast, the stimulation of miR-141 was much weaker [up to 1.5-fold, p>0.05]. With regard to the release into culture medium, a similar picture was observed except for PCA3. PCA3 was below the detection level despite its high stimulation. DHT treatment led to a significant release of PSA-mRNA [up to 12-fold]. Similar to its induction pattern in LNCaP cells, miR-141 was released at a limited quantity into the medium [up to 1.7- fold, p=0.07]. In plasma, only PCA3 differed significantly between the patients and healthy subjects [p=0.001]. Our findings indicate that PCa-related RNA molecules respond differentially to androgen stimulation suggesting differential regulation by androgens

Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients

The X-ray repair cross-complementing group 1 (XRCC1) gene is believed to play an important role in base excision repair and displays genetic polymorphisms. Data on the role of XRCC1 polymorphisms in cancer susceptibility is inconsistent. In the present study, we investigated the effect of two XRCC1 polymorphisms, Arg194Trp and Arg399Gln, on breast cancer risk in a case- control study involving Turkish breast cancer patients and healthy women. Both alleles exhibited a similar distribution among cases and controls leading to lack of any significant association between the XRCC1 polymorphisms and breast cancer risk, either in homozygotes and heterozygotes or combined. The allele frequency of the codon 194 variant was very low in cases and healthy individuals (5.3 and 3.9%, respectively) compared to that of the variant 399Gln allele (39.7 and 37.4%). Our results do not support evidence for a role of the XRCC1 polymorphism in developing breast cancer.

Vitamin D receptor gene polymorphisms in breast cancer

Breast cancer is the leading cause of cancer death among women around the world and its incidence is annually increasing. The vitamin D receptor (VDR) gene is a member of the nuclear receptor superfamily, which is expressed in breast tissue and known to modulate the rate of cell proliferation. Association between the VDR gene polymorphisms and cancer development has been suggested by several studies. However, the relationship between VDR polymorphisms and breast cancer is controversial and has not been confirmed by all studies. The purpose of this study was to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polymorphisms with breast cancer in Turkish patients. In this study, 78 patients with breast cancer and 27 healthy individuals were enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients with breast cancer was similar to that in the normal population. Our data indicate that no significant differences exist between the patients and control subjects.