| Inactivation of a c-Myb/estrogen receptor fusion protein in transformed primary cells leads to granulocyte/macrophage differentiation and down regulation of c-kit but not c-myc or cdc2. | |
MedLine Citation:
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PMID: 9416832 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Primary murine fetal hemopoietic cells were transformed with a fusion protein consisting of the ligand-binding domain of the estrogen receptor and a carboxyl-terminally truncated c-Myb protein (ERMYB). The ERMYB-transformed hemopoietic cells exhibit an immature myeloid phenotype when grown in the presence of beta-estradiol. Upon removal of beta-estradiol, the ERMYB cells display increased adherence, decreased clonogenicity and differentiate to cells exhibiting granulocyte or macrophage morphology. The expression of the c-myc, c-kit, cdc2 and bcl-2 genes, which are putatively regulated by Myb, was investigated in ERMYB cells grown in the presence or absence of beta-estradiol. Neither c-myc nor cdc2 expression was down-regulated after removal of beta-estradiol demonstrating that differentiation is not a consequence of decreased transactivation of these genes by ERMYB. While bcl-2 expression was reduced by 50% in ERMYB cells grown in the absence of beta-estradiol, there was no increase in DNA laddering, suggesting that Myb was not protecting ERMYB cells from apoptosis. In contrast, a substantial (200-fold) decrease in c-kit mRNA level was observed following differentiation of ERMYB cells, and c-kit mRNA could be partially re-induced by the re-addition of beta-estradiol. Furthermore, a reporter construct containing the c-kit promoter was activated when cotransfected with a Myb expression vector, providing further evidence of a role for Myb in the regulation of c-kit. |
Authors:
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A Hogg; S Schirm; H Nakagoshi; P Bartley; S Ishii; J M Bishop; T J Gonda |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 15 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1998-01-15 Completed Date: 1998-01-15 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2885-98 Citation Subset: IM |
Affiliation:
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Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Cell Differentiation / drug effects, genetics Cell Division / drug effects Cell Line, Transformed DNA / biosynthesis, chemistry Down-Regulation / genetics* Estradiol / deficiency, physiology Fetus Genes, cdc* Genes, myc* Genetic Vectors / chemical synthesis Granulocytes / cytology* Hematopoietic Stem Cells Macrophages / cytology* Mice Mice, Inbred CBA Proto-Oncogene Proteins / biosynthesis, genetics*, metabolism Proto-Oncogene Proteins c-kit / genetics* Proto-Oncogene Proteins c-myb RNA, Messenger / biosynthesis, chemistry Receptors, Estrogen / biosynthesis, genetics*, metabolism Recombinant Fusion Proteins / biosynthesis, metabolism* Retroviridae / genetics Trans-Activators / biosynthesis, genetics*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; 0/Trans-Activators; 50-28-2/Estradiol; 9007-49-2/DNA; EC 2.7.10.1/Proto-Oncogene Proteins c-kit |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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