title: Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line.
abstract: The Forkhead box protein M1 (FoxM1) is an important transcription factor having significant roles in various cellular events. FoxM1 overexpression has been reported to be related with many types of cancer. However, it is not known whether it contributes to oncogenesis of acute lymphoblastic leukemia. Siomycin A, a thiazol antibiotic, is known to inhibit FoxM1 transcriptional activity. In this study, we aimed to determine gene expression levels of FoxM1 in Jurkat cells (T-cell acute lymphoblastic leukemia cell line) and therapeutic potential of targeting FoxM1 by siomycin A alone and in combination with dexamethasone which improves the survival of children with T-cell acute lymphoblastic leukemia (ALL). We also examined the molecular mechanisms of siomycin A and dexamethasone-induced cell death in Jurkat cells. We demonstrated that FoxM1 mRNA is highly expressed in Jurkat cells. Dexamethasone and siomycin A caused a significant reduction in gene expression levels of FoxM1 in Jurkat cells. Targeting FoxM1 by siomycin A and dexamethasone caused a significant decrease in T-ALL cell line proliferation through induction of G1 cell cycle arrest. All these findings suggest a possible role of FoxM1 in T-cell ALL pathogenesis and represent FoxM1 as an attractive target for T-cell ALL therapy.
authors.affiliation: Dokuz Eylül University, Faculty of Medicine, Department of Pediatric Hematology, Balçova, Izmir, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Tüfekçi
authors.affiliation: Izmir Institute of Technology, Faculty of Science, Department of Molecular Biology and Genetics, Urla, Izmir, Turkey.
authors.forename: Melis Kartal
authors.initials: MK
authors.lastname: Yandım
authors.affiliation: Dokuz Eylül University, Faculty of Medicine, Department of Pediatric Hematology, Balçova, Izmir, Turkey. Electronic address: hale.oren@deu.edu.tr.
authors.forename: Hale
authors.initials: H
authors.lastname: Ören
authors.affiliation: Dokuz Eylül University, Faculty of Medicine, Department of Pediatric Hematology, Balçova, Izmir, Turkey.
authors.forename: Gülersu
authors.initials: G
authors.lastname: İrken
authors.affiliation: Izmir Institute of Technology, Faculty of Science, Department of Molecular Biology and Genetics, Urla, Izmir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Baran
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D010455:Peptides; D012333:RNA, Messenger; C025311:siomycin; D003907:Dexamethasone
keywords: Dexamethasone; FoxM1; Jurkat cells; Siomycin A; T-cell acute lymphoblastic leukemia