| RRC ID |
43459
|
| 著者 |
Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G, Yabe M, Asai S, Ono R, Nosaka T, Sugita K, Morimoto A, Hayashi Y, Hotta T, Ando K, Miyachi H.
|
| タイトル |
C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene.
|
| ジャーナル |
Oncogene
|
| Abstract |
CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPalpha and C/EBPepsilon. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPalpha or C/EBPepsilon was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPalpha-ER, but not vice versa, thus suggesting that C/EBPepsilon may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPepsilon, as well as C/EBPalpha, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.
|
| 巻・号 |
27(53)
|
| ページ |
6749-60
|
| 公開日 |
2008-12-4
|
| DOI |
10.1038/onc.2008.285
|
| PII |
onc2008285
|
| PMID |
18776924
|
| MeSH |
CCAAT-Enhancer-Binding Protein-alpha / biosynthesis*
CCAAT-Enhancer-Binding Protein-alpha / genetics
CCAAT-Enhancer-Binding Proteins / biosynthesis*
CCAAT-Enhancer-Binding Proteins / genetics
Cell Differentiation*
Cell Line, Tumor
Down-Regulation
Histone-Lysine N-Methyltransferase
Humans
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism
Monocytes / metabolism*
Myeloid-Lymphoid Leukemia Protein / biosynthesis*
Myeloid-Lymphoid Leukemia Protein / genetics
Oncogene Proteins, Fusion / biosynthesis*
Oncogene Proteins, Fusion / genetics
Protein Isoforms / genetics
Protein Isoforms / metabolism
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
|
| IF |
7.971
|
| 引用数 |
14
|
|
WOS 分野
|
GENETICS & HEREDITY
ONCOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189) |
