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Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/7743
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Title: Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.
Authors: Rubio, M.A.
Lopez-Rodriguez, C.
Nueda, A.
Aller, P.
Armesilla, Angel Luis
Vega, Miguel A.
Corbí, A.L.
Citation: Blood, 86(10): 3715-3724
Publisher: American Society of Hematology
Issue Date: 1995
URI: http://hdl.handle.net/2436/7743
PubMed ID: 7579338
Additional Links: http://www.bloodjournal.org/cgi/reprint/86/10/3715
Abstract: To analyze the activity of the CD11c promoter during myeloid differentiation without the limitations of transient expression systems, we have stably transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which the expression of the firefly luciferase cDNA is driven by the CD11c promoter region -361/+43, previously shown to confer myeloid specificity to reporter genes. The stable transfectants (U937-C361) retained the ability to differentiate in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361 differentiation correlated with increased cellular luciferase levels, showing the inducibility of the CD11c promoter during myeloid differentiation and establishing the U937-C361 cells as a suitable system for studying the myeloid differentiation-inducing capacity of cytokines, growth, factors, and other biological response modifiers. Unexpectedly, the inducibility of the CD11c gene promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF-triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in enhancing both the CD11c promoter activity and the cell surface expression of p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c promoter inducibility during PMA- or SB-triggered differentiation, and the dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an intact AP-1-binding site located at -60. These results, together with the lack of functional effect of mutations disrupting the Sp1-and Myb-binding sites within the proximal region of the CD11c promoter, indicate that the myeloid differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate a distinct set of transcription factors and show that the myeloid differentiation-inducibility of the CD11c gene maps to the -99/-53 proximal region of the promoter.
Type: Article
Language: en
Keywords: CD11c integrin gene promoter
Phorbol ester
Sodium butyrate
Cell differentiation
Granulocyte-macrophage
ISSN: 0006-4971
Appears in Collections: Molecular Pharmacology Research Group

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