Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 44Citation - Scopus: 42Inflammation-Mediated Abrogation of Androgen Signaling: an in Vitro Model of Prostate Cell Inflammation(John Wiley and Sons Inc., 2014) Debeleç Bütüner, Bilge; Alapınar, Cansu; Varışlı, Lokman; Erbaykent Tepedelen, Burcu; Hamid, Syed Muhammad; Gönen Korkmaz, Ceren; Korkmaz, Kemal SamiAs a link between inflammation and cancer has been reported in many studies, we established an in vitro model of prostatic inflammation to investigate the loss of androgen receptor (AR)-mediated signaling in androgen responsive prostate cell lines. First, the U937 monocyte cell line was differentiated into macrophages using phorbol acetate (PMA), and cells were induced with lipopolysaccharide (LPS) for cytokine secretion. Next, the cytokine levels (TNFα, IL-6, and IL1β) in conditioned media (CM) were analyzed. Prostate cells were then fed with CM containing varying concentrations of TNFα, and IkB degradation, nuclear factor kappa B (NFκB) translocation and transactivation, and the expression of matrix metalloproteinase-8 (MMP8) and matrix metalloproteinase-9 (MMP9) were then assessed. As a result of CM treatment, ubiquitin-mediated AR degradation, which was restored using anti-TNFα antibody neutralization, led to both a decrease in KLK4, PSA, and NKX3.1 expression levels and the upregulation of GPX2. In addition to the loss of AR, acute and chronic CM exposure resulted in p53 degradation and consequent p21 downregulation, which was also restored by either androgen administration or ectopic NKX3.1 expression via the stabilization of MDM2 levels in LNCaP cells. Additionally, CM treatment enhanced H2AX(S139) phosphorylation (a hallmark of DNA damage) and genetic heterogeneity in the absence of androgens in prostate cells without activating mitochondrial apoptosis. Thus, the data suggest that inflammatory cytokine exposure results in the loss of AR and p53 signaling in prostate cells and facilitates genetic heterogeneity via ROS accumulation to promote prostate carcinogenesis.Article Citation - WoS: 12Citation - Scopus: 12Decreased Expression of Efs Is Correlated With the Advanced Prostate Cancer(SAGE Publications Inc., 2015) Sertkaya, Selda; Hamid, Syed Muhammad; Dilsiz, Nihat; Varışlı, LokmanProstate cancer is the most frequently diagnosed malignant neoplasm in men in the developed countries. Although the progression of prostate cancer and the processes of invasion and metastasis by tumor cells are comparatively well understood, the genes involved in these processes are not fully determined. Therefore, a common area of research interest is the identification of novel molecules that are involved in these processes. In the present study, we have used in silico and experimental approaches to compare the expression of embryonal Fyn-associated substrate (EFS) between normal prostate and prostate cancer. We showed that EFS expression is remarkably downregulated in prostate cancer cells, compared to normal prostate cells. We also found that decreased expression of EFS in prostate cancer cells is due to DNA methylation. In addition, we showed that high EFS expression is important to suppress a malignant behavior of prostate cancer cells. Therefore, we suggest that EFS should be considered as a novel tumor suppressor gene in prostate cancer.