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Öğe Oxidative stress shapes breast cancer phenotype through chronic activation of ATM-dependent signaling(Springer New York LLC, 2015) Alpay, M.; Backman, L.R.F.; Cheng, X.; Dukel, M.; Kim, W.J.; Ai, L.; Brown, K.D.Reactive oxygen species (ROS) are thought to be among the initiating insults that drive carcinogenesis; however, beyond the mutagenic properties of ROS, it is unclear how reactive oxygen species and response to redox imbalance may shape cancer phenotype. We have previously observed that basal activity of the powerfully oncogenic transcription factor NF-?B in cultured breast cancer and other tumor cell lines is dependent upon the DNA damage-responsive kinase ATM. Here we show that, in MDA-MB-231 and HeLa cells, basal ATM-dependent NF-?B activation occurs through a canonical DNA damage-responsive signaling pathway as knockdown of two proteins involved in this signaling pathway, ERC1 and TAB1, results in loss of NF-?B basal activity. We further show that knockdown of ATM in MDA-MB-231, a breast cancer line with a pronounced mesenchymal phenotype, results in the reversion of these cells to an epithelial morphology and gene expression pattern. Culture of MDA-MB-231 and HeLa cells on the antioxidant N-acetyl cysteine (NAC) blunted NF-?B transcriptional activity, and long-term culture on low doses of NAC resulted in coordinate reductions in steady-state ROS levels, acquisition of an epithelial morphology, as well as upregulation of epithelial and downregulation of mesenchymal marker gene expression. Moreover, these reversible effects are attributable, at least in part, to downregulation of ATM-dependent NF-?B signaling in MDA-MB-231 cells as RNAi-mediated knockdown of the NF-?B subunit RelA or its upstream activator TG2 produced similar alterations in phenotype. We conclude that chronic activation of ATM in response to persistent ROS insult triggers continual activation of the oncogenic NF-?B transcriptional complex that, in turn, promotes aggressive breast cancer phenotype. © 2015, Springer Science+Business Media New York.Öğe The relationship between attachment and serum oxytocin and heat shock protein-70 levels in adolescents of parents with schizophrenia and bipolar disorder(Medicinska Naklada Zagreb, 2023) Öz, B.O.; Alpay, M.; Kaban, Ş.Ö.; Sungur, M.A.; Atao?lu, A.Background: The aim of this study was to evaluate serum heat shock protein 70 (HSP70) and oxytocin levels, attachment and perceived social support levels in adolescents with parental bipolar disorder (BD) and Schizophrenia (SCZ). Subjects and Methods: This study included 9 adolescents with SCZ parents, 30 adolescents with BD parents and 31 healthy adolescents. Brief Symptom Inventory (BSI), Relationship Scale Questionnaire-Adolescent Form (RSQ-A) and Multidimensional Scale of Perceived Social Support (MSPSS) were administered to all participants. In addition, serum HSP-70 and oxytocin levels were evaluated. Results: There was no significant difference between the groups in terms of attachment style, psychiatric symptoms and perceived social support. Serum HSP-70 levels were found to be lower in adolescents whose parents had BD. Serum oxytocin levels of the SCZ group were significantly lower than those of the BD group. Conclusions: HSP-70 level was found to be lower in adolescents with BD parents. Oxytocin level was found to be lower in adolescents with SCZ parents. These findings suggest that HSP-70 and oxytocin may be a marker of early life stress in adolescents with parental psychopathology. However, studies are needed to evaluate the relationship between attachment, oxytocin and HSP-70 in adolescents exposed to parental psychopathology in early life. © 2023 Medicinska naklada & Pro mente, Zagreb, Croatia.Öğe Senescence Model Theories from In Vitro through In Vivo(Duzce University Medical School, 2024) Alpay, M.The theoretical equivalence of expressing that a cell is aging to its inability to perform the assumed function is not exactly accurate, it involves a gradual decrease in cell aging mechanisms. Factors such as genetics, lifestyle, and environmental effects maintain the biological change of the cell. The concept of cellular senescence was initially introduced by Hayflick and his collaborators in 1961 when they noticed that human diploid fibroblasts cultured in vitro could undergo only a limited number of cell divisions before their ability to proliferate was permanently halted. This phenomenon, known as the 'Hayflick limit', was subsequently linked to the gradual shortening of telomeres with each successive round of cell division. Throughout the aging process, senescent cells collect in different tissues. Their involvement in age-related health issues such as neurodegenerative disorders, heart problems, cancer, kidney-related changes, chronic lung diseases, and osteoarthritis suggests that targeting senescent cells therapeutically could be promising across various health conditions. This review will discuss the available data on which cell types may undergo aging based on biological aging and how these processes may impact age-associated tissue-specific pathologies. Additionally, the markers used to characterize the physiological transition of aging cells from in vitro to in vivo settings will be evaluated. The discussed data may serve as a significant starting point for an expanded definition of the molecular and functional characteristics of aging cells in different organs, thus supporting the development and enhancement of targeting strategies in vivo. © 2024, Duzce University Medical School. All rights reserved.
