Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).

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 tran...

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Main Authors: Karine Z Oben, Beth W Gachuki, Sara S Alhakeem, Mary K McKenna, Ying Liang, Daret K St Clair, Vivek M Rangnekar, Subbarao Bondada
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5230770?pdf=render
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author Karine Z Oben
Beth W Gachuki
Sara S Alhakeem
Mary K McKenna
Ying Liang
Daret K St Clair
Vivek M Rangnekar
Subbarao Bondada
author_facet Karine Z Oben
Beth W Gachuki
Sara S Alhakeem
Mary K McKenna
Ying Liang
Daret K St Clair
Vivek M Rangnekar
Subbarao Bondada
author_sort Karine Z Oben
collection DOAJ
description 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.
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spelling doaj.art-4bcd361048fb4b30a37263d3c348d29a2022-12-22T03:54:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016976710.1371/journal.pone.0169767Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).Karine Z ObenBeth W GachukiSara S AlhakeemMary K McKennaYing LiangDaret K St ClairVivek M RangnekarSubbarao BondadaAn 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.http://europepmc.org/articles/PMC5230770?pdf=render
spellingShingle Karine Z Oben
Beth W Gachuki
Sara S Alhakeem
Mary K McKenna
Ying Liang
Daret K St Clair
Vivek M Rangnekar
Subbarao Bondada
Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
PLoS ONE
title Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
title_full Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
title_fullStr Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
title_full_unstemmed Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
title_short Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).
title_sort radiation induced apoptosis of murine bone marrow cells is independent of early growth response 1 egr1
url http://europepmc.org/articles/PMC5230770?pdf=render
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AT marykmckenna radiationinducedapoptosisofmurinebonemarrowcellsisindependentofearlygrowthresponse1egr1
AT yingliang radiationinducedapoptosisofmurinebonemarrowcellsisindependentofearlygrowthresponse1egr1
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