Person: ÖZER, SIDIKA AYŞE
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ÖZER
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SIDIKA AYŞE
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Publication Open Access Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments(MDPI AG, 2015-11-10) GÜLLÜ AMURAN, GÖKÇE; Akkiprik, Mustafa; Peker, Irem; Ozmen, Tolga; Amuran, Gokce Gullu; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, AyseIGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.Publication Open Access Multifunctional roles of insulin-like growth factor binding protein 5 in breast cancer(BMC, 2008-08) AKKİPRİK, MUSTAFA; Akkiprik, Mustafa; Feng, Yumei; Wang, Huamin; Chen, Kexin; Hu, Limei; Sahin, Aysegul; Krishnamurthy, Savitri; Ozer, Ayse; Hao, Xishan; Zhang, WeiThe insulin-like growth factor axis, which has been shown to protect cells from apoptosis, plays an essential role in normal cell physiology and in cancer development. The family of insulin-like growth factor binding proteins (IGFBPs) has been shown to have a diverse spectrum of functions in cell growth, death, motility, and tissue remodeling. Among the six IGFBP family members, IGFBP-5 has recently been shown to play an important role in the biology of breast cancer, especially in breast cancer metastasisPublication Open Access Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women(WILEY, 2017-09) GÜLLÜ AMURAN, GÖKÇE; Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Amuran, Gokce Gullu; Ozmen, Tolga; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, AyseBackgroundBoth insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. MethodsTelomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. ResultsTelomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. ConclusionThese results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.Publication Open Access Molecular screening and the clinical impacts of BCR-ABL KD mutations in patients with imatinib-resistant chronic myeloid leukemia(SPANDIDOS PUBL LTD, 2017-12-13) TUĞLULAR, AYŞE TÜLİN; Kockan, Betul; Toptas, Tayfur; Atagunduz, Isik; Tuglular, Ayse Tulin; Ozer, Ayse; Akkiprik, MustafaThe present study aimed to detect the frequency of kinase domain (KD) mutations in order to evaluate their clinical significance and functional importance in 45 patients with chronic myeloid leukemia (CML) who were resistant to imatinib therapy. Sanger sequencing was used (45 patients), along with allele-specific oligonucleotide polymerase chain reaction (ASO-PCR; 3 patients), for the screening of mutations. BCR/ABL KD was amplified by nested PCR and sequencing was performed. Secondly, ASO-PCR was performed to confirm the results of the sequence analysis for E255K mutations. Mutations were detected in 11/45 patients (24.44%) via Sanger sequencing. D241G (4.4%), C369C (4.4%), K285N (2.2%), A380T (2.2%) and A366V (2.2%) mutations were detected. E255K (8.8%) was detected by ASO-PCR and Sanger sequencing. Mutations are a primary reason for suboptimal responses, loss of response and resistance to imatinib. In particular, the E255K mutation, which is characterized by resistance to imatinib and nilotinib, was detected in four patients. Analyzing the mutations and monitoring patients with CML may improve their prognosis and survival rate. ASO-PCR assays will be beneficial for the routine monitoring of mutations.Publication Open Access A novel approach for rapid screening of mitochondrial D310 polymorphism(BMC, 2006-12) GÜLLÜOĞLU, MAHMUT BAHADIR; Aral, C; Kaya, H; Ataizi-Celikel, C; Akkiprik, M; Sonmez, O; Gulluoglu, BM; Ozer, ABackground: Mutations in the mitochondrial DNA ( mtDNA) have been reported in a wide variety of human neoplasms. A polynucleotide tract extending from 303 to 315 nucleotide positions (D310) within the non-coding region of mtDNA has been identified as a mutational hotspot of primary tumors. This region consists of two polycytosine stretches interrupted by a thymidine nucleotide. The number of cytosines at the first and second stretches are 7 and 5 respectively, according to the GeneBank sequence. The first stretch exhibits a polymorphic length variation (6-C to 9-C) among individuals and has been investigated in many cancer types. Large-scale studies are needed to clarify the relationship between cytosine number and cancer development/progression. However, time and money consuming methods such as radioactivity-based gel electrophoresis and sequencing, are not appropriate for the determination of this polymorphism for large case-control studies. In this study, we conducted a rapid RFLP analysis using a restriction enzyme, BsaXI, for the single step simple determination of 7-C carriers at the first stretch in D310 region. Methods: 25 colorectal cancer patients, 25 breast cancer patients and 41 healthy individuals were enrolled into the study. PCR amplification followed by restriction enzyme digestion of D310 region was performed for RFLP analysis. Digestion products were analysed by agarose gel electrophoresis. Sequencing was also applied to samples in order to confirm the RFLP data. Results: Samples containing 7-C at first stretch of D310 region were successfully determined by the BsaXI RFLP method. Heteroplasmy and homoplasmy for 7-C content was also determined as evidenced by direct sequencing. Forty-one percent of the studied samples were found to be BsaXI positive. Furthermore, BsaXI status of colorectal cancer samples were significantly different from that of healthy individuals. Conclusion: In conclusion, BsaXI RFLP analysis is a simple and rapid approach for the single step determination of D310 polymorphism of mitochondrial DNA. This method allows the evaluation of a significant proportion of samples without the need for sequencing- and/or radioactivity-based techniques.