2006 Fiscal Year Final Research Report Summary
The functional role of DAN and p53 family genes in neuroblastoma differentiation induced by BMP.
| Project/Area Number |
17591128
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
NAKAMURA Yohko Chiba Cancer Center Research Institute, Division of Biochemistry, Research Fellow, 生化学研究部, 上席研究員 (60260254)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Neuroblastoma / p53 / Cell Growth Inhibition / BMP |
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| Research Abstract |
Purpose : p53 contains three nuclear localization signals (NLS I, II, III) in its COOH-terminal region. In contrast to other human tumors, p53 is rarely mutated in neuroblastomas. In a recent report, it has been understood that the mutation of p53 exists in about 2% of neuroblastomas. We found p53 mutation in 6 of 30 primary neuroblastoma samples and analyzed p53 and apoptosis-related molecules in BMP-or cisplatin (CDDP)-treated neuroblastomas. In this study, we identified a novel p53 mutant homozygously deleted in SK-N-AS neuroblastoma cells and analyzed its function.
Methods and Results : SH-SY5Y and SK-N-AS cells were treated with CDDP. Their viabilities and apoptotic cell death were investigated by MTT assays, TUNEL assays and FACS analysis. Cell viability was decreased in CDDP-treated SH-SY5Y cells. A higher number of TUNEL-positive and of sub-G0/G1 population cells were observed in CDDP-treated SH-SY5Y cells whereas cisplatin treatment led to the cell cycle arrest in SK-N-AS cells
… More
. p53 was stabilized and phosphorylated at Ser-15 in SH-SY5Y cells exposed to CDDP. Expression of p21^<WAF1>, Box and PUMA were induced in SH-SY5Y cells treated with CDDP whereas only p21^<WAF1> was induced in CDDP-treated SK-N-AS cells. The genome structure of p53 in SK-N-AS was analyzed by the RT-PCR analysis, the PCR analysis and array CGH analysis. As a result, a 3' part of the p53 genomic locus was homozygously deleted in SK-N-AS cells. We found p53 deletion mutant protein with a relative molecular mass of 49 KDa in SK-N-AS cells. Structural analysis revealed that the C-terminal deleted p53 lacks a part of the oligomerization domain as well as nuclear localization signals. The C-terminal deleted p53 was dominantly expressed in cytoplasm and lost the transactivation function. Thus, our present findings suggest that p53 plays an important role in the DNA-damage response in certain neuroblastoma cells and it seems to be important to search for p53 mutations outside of DNA-binding domain. Less
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[Journal Article] topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage.2005
Author(s)
Lin L, Ozaki T, Takada Y, Kageyama H, Nakamura Y, Hata A, Zhang JH, Simonds WF, Nakagawara A, Koseki H.
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Journal Title
Oncogene 24
Pages: 3385-3396
Description
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[Journal Article] Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas.2005
Author(s)
Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A, Hirata T, Kubo H, Goto T, Yamada S, Yoshida Y, Fuchioka M, Ishii S, Nakagawara A.
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Journal Title
Cancer Cell 7
Pages: 337-350
Description
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