Necla Birgül-İyison

Publications (3)8.81 Total impact

• Source

  Available from: PubMed Central

  Article: MENA is a transcriptional target of the Wnt/beta-catenin pathway.

  Ayaz Najafov, Tuncay Seker, Ipek Even, Gerta Hoxhaj, Osman Selvi, Duygu Esen Ozel, Ahmet Koman, Necla Birgül-İyison
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  ABSTRACT: Wnt/β-catenin signalling pathway plays important roles in embryonic development and carcinogenesis. Overactivation of the pathway is one of the most common driving forces in major cancers such as colorectal and breast cancers. The downstream effectors of the pathway and its regulation of carcinogenesis and metastasis are still not very well understood. In this study, which was based on two genome-wide transcriptomics screens, we identify MENA (ENAH, Mammalian enabled homologue) as a novel transcriptional target of the Wnt/β-catenin signalling pathway. We show that the expression of MENA is upregulated upon overexpression of degradation-resistant β-catenin. Promoters of all mammalian MENA homologues contain putative binding sites for Tcf4 transcription factor--the primary effector of the Wnt/β-catenin pathway and we demonstrate functionality of these Tcf4-binding sites using luciferase reporter assays and overexpression of β-catenin, Tcf4 and dominant-negative Tcf4. In addition, lithium chloride-mediated inhibition of GSK3β also resulted in increase in MENA mRNA levels. Chromatin immunoprecipitation showed direct interaction between β-catenin and MENA promoter in Huh7 and HEK293 cells and also in mouse brain and liver tissues. Moreover, overexpression of Wnt1 and Wnt3a ligands increased MENA mRNA levels. Additionally, knock-down of MENA ortholog in D. melanogaster eyeful and sensitized eye cancer fly models resulted in increased tumor and metastasis formations. In summary, our study identifies MENA as novel nexus for the Wnt/β-catenin and the Notch signalling cascades.
  PLoS ONE 01/2012; 7(5):e37013. · 4.09 Impact Factor
• Article: Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets.

  Ersen Kavak, Ayaz Najafov, Nuri Ozturk, Tuncay Seker, Kader Cavusoglu, Tolga Aslan, Adil Doganay Duru, Tahsin Saygili, Gerta Hoxhaj, Mahmut Can Hiz, Durisehvar Ozer Unal, Necla Birgül-Iyison, Mehmet Ozturk, Ahmet Koman
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  ABSTRACT: The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. beta-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated by active beta-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low beta-catenin/TCF activities. High TCF activity Huh7 cells led to earlier and larger tumor formation when xenografted into nude mice. SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis were performed in parallel, to compare gene expression between low and high beta-catenin/TCF activity clones, and also those that had been rescued from the xenograft tumors. SAGE and genome-wide microarray data were compared and contrasted. BRI3 and HSF2 were identified as novel targets of Wnt/beta-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment.
  Cellular signalling 10/2010; 22(10):1523-35. · 4.09 Impact Factor
• Source

  Available from: turkishneurosurgery.org.tr

  Article: Prenatal expressions of hyperpolarization-activated cyclic-nucleotide-gated channel (HCN) genes in dysplastic hippocampi in rats.

  Cihan Işler, Taner Tanriverdi, Ersen Kavak, Galip Zihni Sanus, Mustafa Onur Ulu, Gözde Erkanli, Ahmet Koman, Necla Birgül Iyison, Mustafa Uzan
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  ABSTRACT: Hyperpolarization-activated cyclic nucleotide-gated (HCN or h-channel) channels mediate hyperpolarization-activating currents in the hippocampus and neocortex. The aim of this study is to present prenatal h-channel gene expressions (HCN1 and HCN2; HCN1-Entrez-Gene ID: 84390; HCN2- Entrez Gene ID: 114244) in dysplastic hippocampal pyramidal neurons induced by in utero irradiation in rats. MATERIALS and Time-pregnant Wistar albino rats were irradiated and the dysplastic hippocampus in their 2 month-old litters was studied. Gene expression was studied by RNA extraction and polymerase chain reaction methods. None of the rats showed seizure activity. mRNA levels of HCN1 and HCN2 genes were decreased especially in the CA1 and CA3 pyramidal neurons in the hippocampi of experimental rats; however, the differences were not significant compared to controls. In CA2, mRNA levels of both genes were increased and this rise did not reach significant level. The CA4 sub-region showed a different pattern of expression: HCN1 increased but HCN2 decreased insignificantly compared to controls. Our results demonstrated that dysplastic neurons showed decreased levels of mRNA expression of HCN1 and HCN2 genes, in particularly CA1 and CA3 pyramidal neurons. The rationale for how these changes contribute to epileptogenesis in dysplastic tissues still requires further studies.
  Turkish neurosurgery 02/2008; 18(4):327-35. · 0.62 Impact Factor