PPAR ? activators induce growth arrest and process extension in B12 oligodendrocyte-like cells and terminal differentiation of cultured oligodendrocytes

2003 ◽  
Vol 72 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Alejandro D. Roth ◽  
Andrea V. Leisewitz ◽  
Juan E. Jung ◽  
Patricia Cassina ◽  
Luis Barbeito ◽  
...  
Keyword(s):  
Growth Arrest ◽  
Terminal Differentiation ◽  
Induce Growth Arrest

scholarly journals Batf Promotes Growth Arrest and Terminal Differentiation of Mouse Myeloid Leukemia Cells

2011 ◽  
Vol 9 (3) ◽  
pp. 350-363 ◽  
Author(s):  
Juan Liao ◽  
Sean E. Humphrey ◽  
Stacie Poston ◽  
Elizabeth J. Taparowsky
Keyword(s):  
Myeloid Leukemia ◽  
Growth Arrest ◽  
Terminal Differentiation ◽  
Leukemia Cells

Abstract 1031: Nuclear relocalization of NPM1c induces terminal differentiation and cell growth arrest

2017 ◽  
Author(s):  
Lorenzo Brunetti ◽  
Michael C. Gundry ◽  
Anna G. Guzman ◽  
Ilaria Gionfriddo ◽  
Federica Mezzasoma ◽  
...  
Keyword(s):  
Cell Growth ◽  
Growth Arrest ◽  
Terminal Differentiation ◽  
Cell Growth Arrest

A Critical Role for the Bcl-2 Pathway in Notch-Mediated B Cell Apoptosis, Where Growth Arrest Is Independent of the E2A, IL-3 and p21Waf1/p27Kip1 Pathways.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 237-237 ◽  
Author(s):  
Patrick A. Zweidler-McKay ◽  
Julian J. Lum ◽  
Craig B. Thompson ◽  
Warren S. Pear
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Notch Signaling ◽  
Cell Apoptosis ◽  
Therapeutic Approach ◽  
Critical Role ◽  
Growth Arrest ◽  
Model System ◽  
B Cell Malignancies ◽  
Induce Growth Arrest

Abstract The Notch receptor pathway regulates critical cell fate decisions in multiple developmental systems, including hematopoiesis. We have previously demonstrated that Notch signaling induces growth arrest and apoptosis in a wide range of human B cell malignancies and has potential as a B cell-specific therapeutic approach. In order to identify the mechanisms of growth arrest and apoptosis we analyzed an immortalized murine progenitor B cell line derived from Bax/Bak double knockout mice. These cells are unable to undergo apoptosis since they lack the pro-apoptotic effectors of the Bcl-2 pathway, and have been shown to be resistant to multiple apoptotic stimuli. Here we report that induction of Notch signaling through expression of several family members (Notch1, Notch4, Hes1) leads to rapid growth arrest, but not apoptosis, within 48 hours in these Bax-/Bak- progenitor B cells. These findings provide the first evidence for a critical role of the Bcl-2 pathway in Notch-mediated B cell apoptosis, and establish a mitochondrial-dependent mechanism for this effect. Importantly, the kinetics of growth arrest are accelerated with the expression of the Notch downstream target Hes1 as compared to the Notch receptors 1 and 4. These results extend our observation that Hes1 is sufficient to reproduce Notch-mediated B cell death, by demonstrating that Hes1 is more proximal to the critical growth inhibiting events, and may therefore provide a therapeutic target. In this model system we can isolate growth arrest from the effects on the apoptotic cascade. This provides a unique opportunity to explore the mechanism of Notch-mediated growth arrest. Prior studies have suggested that Notch signaling may induce growth arrest through inhibition of the E2A pathway, or through upregulation of the cell cycle regulators p21Waf1 and p27Kip1. In this model system, inhibition of the E2A pathway is not sufficient to induce growth arrest. Similarly, Hes1 does not upregulate either p21Waf1 or p27Kip1, suggesting that this is not the mechanism of growth arrest. To explore whether Notch/Hes1 induce growth arrest through inhibition of the IL-3 pathway, we compared phenotypic and functional aspects of Hes1 expression and IL-3 withdrawal. Although the timing and phenotypic effects (cell size, cell cycle and metabolic studies) were quite similar, Hes1 growth arrested cells lose their ability to migrate in response to the pan-B chemo-attractant SDF1a compared to IL-3 withdrawn cells. In summary, these results demonstrate that Notch/Hes1-mediated B cell apoptosis relies critically on pro-apoptotic members of the Bcl-2 pathway, Bax/Bak. Furthermore, growth arrest when isolated from apoptosis does not rely on inhibition of the E2A or IL-3 pathways, nor upregulation of p21Waf1/ p27Kip1. These findings provide the first insight into the mechanisms of Notch/Hes1-mediated B cell growth arrest and apoptosis and will help guide the development of Notch/Hes1 signaling as a cell-type specific therapeutic approach for B cell malignancies.

Loss of Growth Arrest DNA Damage 45b (GADD45b) Enhances Oncogenicity in BCR/ABL-Induced Chronic Myelogenous Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5337-5337
Author(s):  
Xiaojin Sha ◽  
Barbara Hoffman ◽  
Dan A. Liebermann
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Chronic Myelogenous Leukemia ◽  
Growth Arrest ◽  
Terminal Differentiation ◽  
Myelogenous Leukemia ◽  
M Cell ◽  
Cycle Arrest ◽  
Exogenous Stress ◽  
Myeloid Progenitors

Abstract Growth arrest DNA damage 45b (GADD45b) is upregulated during myeloid lineage terminal differentiation. It is also involved in G2/M cell cycle arrest and apoptosis in response to exogenous stress stimuli. To investigate the effect of GADD45b in the development of leukemia, lethally irradiated mice were reconstituted with either wildtype or gadd45b null myeloid progenitors which retrovirally expressed 210-kD BCR/ABL fusion oncoprotein. We found that both wildtype and gadd45b null myeloid progenitors expressing BCR/ABL induced chronic myelogenous leukemia (CML)-like disease between 11days to 22days after bone marrow transplantation in recipients. However, gadd45b null recipients had a shorter latency (11days–19days) compared to those of wildtypes (14days–22days). This result implies that GADD45b acts as a supressor of CML. Data will be presented on further analyzing the phenotypes of these mice.

Synthetic ceramides induce growth arrest or apoptosis by altering cellular redox status

2002 ◽  
Vol 407 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Darren Charles Phillips ◽  
Kirsty Allen ◽  
Helen R Griffiths
Keyword(s):  
Growth Arrest ◽  
Redox Status ◽  
Cellular Redox ◽  
Induce Growth Arrest
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