| RRC ID |
72948
|
| 著者 |
Mori J, Suzuki S, Hara M, Kaneko A, Yamashita K, Kumagai M, Sakuma T, Kakizawa T, Yamazaki M, Takeda T, Miyamoto T, Ichikawa K, Hashizume K.
|
| タイトル |
Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.
|
| ジャーナル |
Jpn J Cancer Res
|
| Abstract |
Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.
|
| 巻・号 |
90(6)
|
| ページ |
660-8
|
| 公開日 |
1999-6-1
|
| DOI |
10.1111/j.1349-7006.1999.tb00798.x
|
| PII |
S091050509980132X
|
| PMID |
10429659
|
| PMC |
PMC5926114
|
| MeSH |
Antineoplastic Agents / pharmacology*
Cell Cycle
Cell Division / drug effects
Chromosome Aberrations
Drug Resistance, Neoplasm
HL-60 Cells
Humans
Macrophage-1 Antigen / analysis
Receptors, Retinoic Acid / analysis
Retinoic Acid Receptor alpha
Retinoid X Receptors
Transcription Factors / analysis
Tretinoin / pharmacology*
Vitamin D / pharmacology
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041) |
