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p53-dependent and -...
p53-dependent and -independent differentiation of leukemic U-937 cells : relationship to cell cycle control
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- Ehinger, Mats (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Pathology, Lund,Section V,Department of Clinical Sciences, Lund
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- Bergh, G (author)
- Lund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Johnsson, E (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups
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- Baldetorp, B (author)
- Lund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,Biomarkörer och Epi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund University Research Groups,Biomarkers and epidemiology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Olsson, I (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Gullberg, U (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups
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(creator_code:org_t)
- 1998
- 1998
- English.
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In: Experimental Hematology. - 1873-2399. ; 26:11, s. 52-1043
- Related links:
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https://lup.lub.lu.s...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- 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
Publication and Content Type
- art (subject category)
- ref (subject category)
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