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p53-dependent and -independent differentiation of leukemic U-937 cells: relationship to cell cycle control

Ehinger, Mats LU ; Bergh, G; Johnsson, E; Baldetorp, Bo LU ; Olsson, Inge LU and Gullberg, Urban LU (1998) In Experimental Hematology 26(11). p.1043-1052
Abstract
Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used... (More)
Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used for mediating G1 arrest. The differentiation response to transfected p53 with or without INF-gamma was inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine) in a dose-dependent manner. In contrast, the differentiation response of p53-negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated differentiation could be achieved in cells arrested in G1 by concomitant incubation with cAMP-inducing agents, indicating that differentiation can occur in the absence of proliferation. In conclusion, the results of this study indicate that p53-dependent and -independent differentiation can occur independently of cell cycle regulation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Hematology
volume
26
issue
11
pages
1043 - 1052
publisher
Elsevier
external identifiers
  • pmid:9766444
  • scopus:0031723096
ISSN
1873-2399
language
English
LU publication?
yes
id
2b94b7c8-67c7-479b-a602-b152d9b157fe (old id 1112835)
date added to LUP
2008-07-11 13:04:06
date last changed
2017-01-01 04:46:56
@article{2b94b7c8-67c7-479b-a602-b152d9b157fe,
  abstract     = {Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used for mediating G1 arrest. The differentiation response to transfected p53 with or without INF-gamma was inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine) in a dose-dependent manner. In contrast, the differentiation response of p53-negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated differentiation could be achieved in cells arrested in G1 by concomitant incubation with cAMP-inducing agents, indicating that differentiation can occur in the absence of proliferation. In conclusion, the results of this study indicate that p53-dependent and -independent differentiation can occur independently of cell cycle regulation.},
  author       = {Ehinger, Mats and Bergh, G and Johnsson, E and Baldetorp, Bo and Olsson, Inge and Gullberg, Urban},
  issn         = {1873-2399},
  language     = {eng},
  number       = {11},
  pages        = {1043--1052},
  publisher    = {Elsevier},
  series       = {Experimental Hematology},
  title        = {p53-dependent and -independent differentiation of leukemic U-937 cells: relationship to cell cycle control},
  volume       = {26},
  year         = {1998},
}