title: Bag-1 promotes cell survival through c-Myc-mediated ODC upregulation that is not preferred under apoptotic stimuli in MCF-7 cells.
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 H2 O2 and aldehydes. Bag-1L+ cells prevented drug-induced PAO activation leading to a decrease in H2 O2 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.
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Ozfiliz
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Tugba
authors.initials: T
authors.lastname: Kizilboga
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Demir
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Alkurt
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul, Turkey.
authors.forename: Narçin
authors.initials: N
authors.lastname: Palavan-Unsal
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Kultur University, Istanbul, Turkey.
authors.forename: Elif Damla
authors.initials: ED
authors.lastname: Arisan
authors.affiliation: Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Dinler-Doganay
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D061986:MCF-7 Cells / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; C091732:BCL2-associated athanogene 1 protein; C481505:BCL2L15 protein, human; D004268:DNA-Binding Proteins; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D009955:Ornithine Decarboxylase; D017239:Paclitaxel; D002945:Cisplatin
keywords: Bag-1; apoptosis; breast cancer; c-Myc; cisplatin; paclitaxel; polyamines