title: Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
abstract: An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis-p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA) nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Karine Z
authors.initials: KZ
authors.lastname: Oben
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Beth W
authors.initials: BW
authors.lastname: Gachuki
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Alhakeem
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Mary K
authors.initials: MK
authors.lastname: McKenna
authors.affiliation: Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, United States of America.|Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.|Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky, United States of America.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Rangnekar
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, Kentucky, United States of America.|Markey Cancer Center, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Subbarao
authors.initials: S
authors.lastname: Bondada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D013977:Tibia / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: D051766:Early Growth Response Protein 1; D006657:Histones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C486109:Egr1 protein, mouse; C475961:gamma-H2AX protein, mouse