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Bag-1 promotes cell survival through c-Myc-mediated ODC upregulation that is not preferred under apoptotic stimuli in MCF-7 cells

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Author
Özfiliz Kılbaş, Pelin
Kızılboğa, Tuğba
Demir, Salih
Palavan Ünsal, Zeynep Narçın
Arısan, Elif Damla
Dinler Doğanay, Gizem
Type
Article
Date
2015-07
Language
en_US
Metadata
Show full item record
Abstract
Bag-1, Bcl-2 associated athanogene-1, is a multifunctional protein that can regulate a wide variety of cellular processes: proliferation, cell survival, transcription, apoptosis and motility. Bag-1 interacts with various targets in the modulation of these pathways; yet molecular details of Bag-1's involvement in each cellular event are still unclear. We first showed that forced Bag-1 expression promotes cell survival and prevents drug-induced apoptosis in MCF-7 breast cancer cells. Increased mRNA expressions of c-myc protooncogene and ornithine decarboxylase (ODC), biosynthetic enzyme of polyamines, were detected in Bag-1L+ cells, and western blots against the protein product of c-Myc and ODC confirmed these findings. Once ODC, a c-Myc target, gets activated, polyamine biosynthesis increases. We observed enhanced polyamine content in the Bag-1L+ cells. On the contrary, when polyamine catabolic mechanisms were investigated, Bag-1 silencing suppressed biosynthesis of polyamines because of the downregulation of ODC and upregulation of PAO. Exposure of cells to apoptotic inducers enhances the cell death mechanism by producing toxic products such as H2O2 and aldehydes. Bag-1L+ cells prevented drug-induced PAO activation leading to a decrease in H2O2 production following cisplatin or paclitaxel treatment. In this line, our results suggested that Bag-1 indirectly affects cell survival through c-Myc activated signalling that causes elevation of ODC levels, leading to an increase of the polyamine content. Copyright (c) 2015 John Wiley & Sons, Ltd.
Subject
Bag-1
c-Myc
Polyamines
Paclitaxel
Cisplatin
Apoptosis
Breast cancer
URI
https://doi.org/10.1002/cbf.3114
https://hdl.handle.net/11413/2065
Collections
  • Makaleler / Articles [140]
  • Pubmed Publications [149]
  • Scopus Publications [724]
  • WoS Publications [1016]

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Hakkında |Politika | Kütüphane | İletişim | Send Feedback | Admin

Istanbul Kültür University, Ataköy Campus E5 Karayolu Üzeri Bakırköy 34158, İstanbul / TURKEY
Copyright © İstanbul Kültür University

Creative Commons Lisansı
IKU Institutional Repository, Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

Designed by  UNIREPOS