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: 7Citation - Scopus: 7Connexin 32 Overexpression Increases Proliferation, Reduces Gap Junctional Intercellular Communication, Motility and Epithelial-To Transition in Hs578t Breast Cancer Cells(Springer, 2022) Uğur, Deniz; Güngül, Taha Buğra; Yücel, Simge; Özçivici, Engin; Yalçın Özuysal, Özden; Meşe Özçivici, GülistanConnexins (Cx) are primary components of gap junctions that selectively allow molecules to be exchanged between adjacent cells, regulating multiple cellular functions. Along with their channel forming functions, connexins play a variety of roles in different stages of tumorigenesis and their roles in tumor initiation and progression is isoform- and tissue-specific. While Cx26 and Cx43 were downregulated during breast tumorigenesis, Cx32 was accumulated in the cytoplasm of the cells in lymph node metastasis of breast cancers and Cx32 was further upregulated in metastasis. Cx32's effect on cell proliferation, gap junctional communication, hemichannel activity, cellular motility and epithelial-to-mesenchymal transition (EMT) were investigated by overexpressing Cx32 in Hs578T and MCF7 breast cancer cells. Additionally, the expression and localization of Cx26 and Cx43 upon Cx32 overexpression were examined by Western blot and immunostaining experiments, respectively. We observed that MCF7 cells had endogenous Cx32 while Hs578T cells did not and when Cx32 was overexpressed in these cells, it caused a significant increase in the percentages of Hs578T cells at the S phase in addition to increasing their proliferation. Further, while Cx32 overexpression did not induce hemichannel activity in either cell, it decreased gap junctional communication between Hs578T cells. Additionally, Cx32 was mainly observed in the cytoplasm in both cells, where it did not form gap junction plaques but Cx32 overexpression reduced Cx43 levels without affecting Cx26. Moreover, migration and invasion potentials of Hs578T and migration in MCF7 were reduced upon Cx32 overexpression. Finally, the protein level of mesenchymal marker N-cadherin decreased while epithelial marker ZO-1 and E-cadherin increased in Hs578T cells. We observed that Cx32 overexpression altered cell proliferation, communication, migration and EMT in Hs578T, suggesting a tumor suppressor role in these cells while it had minor effects on MCF7 cells.Book Part Citation - Scopus: 4Epigenetics of Breast Cancer: Dna Methylome and Global Histone Modifications(Springer, 2016) Meşe, Gülistan; Yalçın Özuysal, ÖzdenBreast cancer, a heterogeneous disease comprised of tumors with different histological characteristics and clinical outcomes, is the leading cause of cancer deaths in women. Heterogeneous nature of the breast cancer demands delicate approaches to diagnose and follow the most appropriate strategy for clinical management. Based on microarray analysis of mRNA expression, four main molecular subtypes were identified: (a) luminal A, (b) luminal B, (c) basal-like, and (d) ERBB2(+). Even though molecular subtypes provided novel insights into our understanding of breast cancer heterogeneity, there is still room for improvement for better diagnostic, prognostic and therapeutic approaches. In this sense, epigenetics, specifically DNA methylation and histone modifications, have emerged as prominent candidates since several epigenetic factors were observed to be recurrently mutated in cancers including breast cancer. Recent advances in the field implicated that DNA methylation profiles and histone modifications are strongly associated with breast tumor subtypes and patient prognosis. Therefore, understanding contributions of epigenetics to breast cancer biology will lead to better diagnostic and prognostic strategies and will enable development of novel therapeutic approaches. © Springer International Publishing Switzerland 2016.