PMID:17353905
| Citation |
Takahashi, M, Ozaki, T, Takahashi, A, Miyauchi, M, Ono, S, Takada, N, Koda, T, Todo, S, Kamijo, T and Nakagawara, A (2007) DFF45/ICAD restores cisplatin-induced nuclear fragmentation but not DNA cleavage in DFF45-deficient neuroblastoma cells. Oncogene 26:5669-73 |
|---|---|
| Abstract |
We have previously defined a homozygously deleted region at chromosome 1p36.2-p36.3 in human neuroblastoma cell lines, NB-1 and NB-C201, and identified six genes including DFF45/ICAD within this region. In this study, we found that NB-C201 cells are much more resistant to various genotoxic stresses such as cisplatin (CDDP) than CHP134 and SH-SY5Y cells that do not have the homozygous deletion. To examine a role(s) of DFF45 in the regulation of apoptosis in response to CDDP, we have established stably DFF45-expressing NB-C201 cell clones (DFF45-1 and DFF45-3) and a control cell clone (NB-C201-C) using a retrovirus-mediated gene transfer. In contrast to NB-C201-C cells, DFF45-3 cells displayed apoptotic nuclear fragmentation in response to CDDP. Although CDDP-induced proteolytic cleavage of procaspase-3 and DFF45 in DFF45-3 cells, we could not detect a typical apoptotic DNA fragmentation. Additionally, deletion analysis revealed that C-terminal region of DFF45 is required for inducing nuclear fragmentation. Unexpectedly, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that DFF45 has undetectable effect on CDDP sensitivity of NB-C201 cells. Taken together, our present results suggest that DFF45/DFF40 system may be sufficient for CDDP-induced nuclear fragmentation but not DNA cleavage. |
| Links |
PubMed Online version:10.1038/sj.onc.1210352 |
| Keywords |
Antineoplastic Agents/pharmacology; Apoptosis/genetics; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Blotting, Northern; Blotting, Western; Cell Line, Tumor; Cell Nucleus/drug effects; Cell Nucleus/genetics; Cell Survival/drug effects; Cisplatin/pharmacology; DNA Cleavage/drug effects; DNA Fragmentation/drug effects; Gene Deletion; Gene Expression Regulation, Neoplastic/drug effects; Humans; Neuroblastoma/genetics; Neuroblastoma/metabolism; Neuroblastoma/pathology; Time Factors; Transfection |
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