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

Ehinger, Mats LU ; Bergh, G LU ; Johnsson, E LU ; Baldetorp, B LU ; Olsson, I LU and Gullberg, U LU (1998) In Experimental Hematology 26(11). p.52-1043
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.

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; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
1-Methyl-3-isobutylxanthine/pharmacology, Antineoplastic Agents/pharmacology, Cell Cycle/genetics, Cell Death/drug effects, Cell Differentiation/drug effects, Cholecalciferol/pharmacology, Colforsin/pharmacology, Cyclic AMP/pharmacology, Genes, p53, Growth Inhibitors/pharmacology, Humans, Interferon-gamma/pharmacology, Leukemia, Monocytic, Acute/genetics, Tretinoin/pharmacology, Tumor Cells, Cultured
in
Experimental Hematology
volume
26
issue
11
pages
52 - 1043
publisher
Elsevier
external identifiers
  • pmid:9766444
  • scopus:0031723096
  • pmid:9766444
ISSN
1873-2399
language
English
LU publication?
yes
id
2b94b7c8-67c7-479b-a602-b152d9b157fe (old id 1112835)
date added to LUP
2016-04-01 12:02:36
date last changed
2024-10-08 19:28:23
@article{2b94b7c8-67c7-479b-a602-b152d9b157fe,
  abstract     = {{<p>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.</p>}},
  author       = {{Ehinger, Mats and Bergh, G and Johnsson, E and Baldetorp, B and Olsson, I and Gullberg, U}},
  issn         = {{1873-2399}},
  keywords     = {{1-Methyl-3-isobutylxanthine/pharmacology; Antineoplastic Agents/pharmacology; Cell Cycle/genetics; Cell Death/drug effects; Cell Differentiation/drug effects; Cholecalciferol/pharmacology; Colforsin/pharmacology; Cyclic AMP/pharmacology; Genes, p53; Growth Inhibitors/pharmacology; Humans; Interferon-gamma/pharmacology; Leukemia, Monocytic, Acute/genetics; Tretinoin/pharmacology; Tumor Cells, Cultured}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{52--1043}},
  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}},
}