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Type: Journal article
Title: 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.
Author: Hogg, A.
Schirm, S.
Nakagoshi, H.
Bartley, P.
Ishii, S.
Bishop, J.
Gonda, T.
Citation: Oncogene, 1997; 15(24):2885-2898
Issue Date: 1997
ISSN: 0950-9232
Abstract: 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.
Keywords: Granulocytes
Hematopoietic Stem Cells
Cell Line, Transformed
Mice, Inbred CBA
Proto-Oncogene Proteins c-myb
Proto-Oncogene Proteins
Receptors, Estrogen
Recombinant Fusion Proteins
RNA, Messenger
Cell Division
Cell Differentiation
Genes, cdc
Genes, myc
Genetic Vectors
Proto-Oncogene Proteins c-kit
DOI: 10.1038/sj.onc.1201472
Appears in Collections:Aurora harvest
Medicine publications

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