Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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Author: search.filters.author.Korkmaz, Kemal SamiSubject: search.filters.subject.Inflammation

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  • Article
    Citation - WoS: 2
    Citation - Scopus: 3
    Nkx3.1 Expression Contributes To Epithelial-Mesenchymal Transition of Prostate Cancer Cells
    (American Chemical Society, 2023) Saydullaeva, Iroda; Debeleç Bütüner, Bilge; Korkmaz, Kemal Sami
    Studies demonstrate that inflammation synergizes with highgrade aggressive prostate tumor development and ultimately metastatic spread, in which a lot of work has been done in recent years. However, the clear mechanism of inflammation inciting prostate cancer remains largely uncharacterized. Our previous study has shown that the conditioned media (CM)-mediated LNCaP cell migration is partially correlated with the loss of expression of the tumor suppressor NKX3.1. Here, we continue to investigate the inflammation-mediated migration of prostate cancer cells, and the role of NKX3.1 in this process to gain insights into cell migration-related changes comprehensively. Earlier, the model of inflammation in the tumor micro environment have been optimized by our research group; here, we continue to investigate the time-dependent effect of CM exposure together with NKX3.1 changes, in which we observed that these changes play important roles in gaining heterogeneous epithelial-to-mesenchymal transition (EMT) phenotype. Hence, this is an important parameter of tumor progression; we depleted NKX3.1 expression using the CRISPR/Cas9 system and examined the migrating cell clusters after exposure to inflammatory cytokines. We found that the migrated cells clearly demonstrate reversible loss of E-cadherin expression, which is consistent with subsequent vimentin expression alterations in comparison to control cells. Moreover, the data suggest that the AR mediated transcriptional program also contributes to mesenchymal-to-epithelial transition (MET) in prostate cancer progression. Furthermore, the quantitative proteomic analysis showed that migrated subpopulations from the same cell line presented different phenotypes in which the proteins overexpressed are involved in cell metabolism and RNA processing. According to KEGG pathway analysis, the ABC transporters were found to be the most significant. Thus, the dynamic process of cellular migration favors diverse genetic compositions under changing tumor microenvironments. The different levels of invasiveness are supported by shifting the cells in between these EMT and MET phenotypes.
  • Article
    Citation - WoS: 44
    Citation - Scopus: 42
    Inflammation-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 Sami
    As 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.