2004 Fiscal Year Final Research Report Summary
Role of p53 family genes in acquiring drug resistance of neuroblastoma.
| Project/Area Number |
15390535
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
NAKAGAWARA Akira Chiba Cancer Center Research Institute, Director, 研究局, 局長 (50117181)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Toshinori Chiba Cancer Center Research Institute, Division of Biochemistry, Researcher, 生化学研究部, 上席研究員 (40260252)
ICHIKAWA Miki (OHIRA Miki) Chiba Cancer Center Research Institute, Division of Biochemistry, Researcher, 生化学研究部, 研究員 (20311384)
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| Project Period (FY) |
2003 – 2004
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| Keywords | p53 / p73 / Mdm2 / multi-drug resistance / BMP2 / neuroblastoma / cDNA microarray |
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| Research Abstract |
We have examined the role of p53 family genes in the genesis and acquisition of multi-drug resistance in human neuroblastoma. The results we obtained are as follows. (1)Mutation of the p53 gene was very rare in primary neuroblastomas obtained at initial surgery. However, it was induced in recurrent tumors as well as in many neuroblastoma cell lines. Among 30 neuroblastoma cell lines, we found 6 loss of function mutations in the p53 gene by yeast functional assay and DNA sequencing. Furthermore, we found that high levels of p53 mRNA expression were significantly associated with poor prognosis of neuroblastoma by using our in-house cDNA microarray which carried 5,300 cDNAs obtained from primary neuroblastoma cDNA libraries we generated. In addition, it is already known that p53 is often localized in cellular cytoplasm in advanced stages neuroblastomas. These suggest that p53 may function in primary neuroblastomas to regulate the tumor growth and apoptosis. (2)We searched for the role of p53 family genes in retinoic acid-induced apoptosis of neuroblastoma cells. However, the levels of p53 family molecules were too low to be detected. Only p73 protein was induced at the protein level. (3)In the panel of human cancer cell lines including neuroblastoma, the levels of p73 and p63 expression were high in the lines with resistance to cisplatin. Our further analysis revealed that Mdm2 expression was high in those cisplatin-resistant cell lines, that in turn induced degradation of p53 protein, leading to acquiring the resistance. Currently, we are further searching for the precise mechanism to develop new therapeutic strategies against aggressive neuroblastomas.
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Research Products
(54 results)
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[Journal Article] LMO3 interacts with neuronal transcription factor, HEN2,and acts as an oncogene in neuroblastoma.2005
Author(s)
Aoyama M, Ozaki T, Inuzuka H, Tomotsune D, Hirato J, Okamoto Y, Tokita H, Ohira M, Nakagawara A.
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Journal Title
Cancer Res. 65
Pages: 4587-4597
Description
「研究成果報告書概要(欧文)」より
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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
「研究成果報告書概要(欧文)」より
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[Journal Article] Topors, a p53 and topoisomerase I-binding RING finger protein, is a co-activator 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 J-H, Simonds W, Nakagawara A. Koseki H.
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Journal Title
Oncogene 24
Pages: 3385-3396
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma.2004
Author(s)
Hiyama E, Yamaoka H, Matsunaga T, Hayashi Y, Ando H, Suita S, Horie H, Kaneko M, Sasaki F, Hashizume K, Nakagawara A. Ohnuma N, Yokoyama T.
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Journal Title
Br.J.Cancer 91
Pages: 972-979
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NEDL1,a novel ubiquitin-protein isopeptide ligase for Dishevelled-1,targets mutant superoxide dismutase-1.2004
Author(s)
Miyazaki K, Fujita T, Ozaki T, Kato C, Kurose Y, Sakamoto M, Kato S, Goto T, Itoyama Y, Aoki M, Nakagawara A.
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Journal Title
J.Biol.Chem. 279
Pages: 11327-11335
Description
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[Journal Article] A novel HECT-type E3 ubiquitin ligase, NEDL2,stabilizes p73 and enhances its transcriptional activity.2003
Author(s)
Miyazaki K, Ozaki T, Kato C, Hanamoto T, Fujita T, Irino S, Watanabe K, Nakagawa T, Nakagawara A.
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Journal Title
Biochem.Biophys.Res.Commun. 308
Pages: 106-113
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression profiling and characterization of 4,200 genes cloned from primary neuroblastomas : Identification of 305 genes differentially expressed between favorable and unfavorable subsets.2003
Author(s)
Ohira M, Morohashi A, Inuzuka H, Shishikura T, Kawamoto T, Kageyama H, Nakamura Y, Isogai E, Takayasu H, Sakiyama S, Suzuki Y, Sugano S, Goto T, Sato S, Nakagawara A.
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Journal Title
Oncogene 22
Pages: 5525-5536
Description
「研究成果報告書概要(欧文)」より
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