2004 Fiscal Year Final Research Report Summary
Clinical significance of oncogenic mutations of p53 gene in oral cancen : Relationship of the mutations with radiation- and chemo-sensitivity
| Project/Area Number |
15592131
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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 |
Surgical dentistry
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| Research Institution | Dokkyo University School of Medicine |
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Principal Investigator |
KAWAMATA Hitoshi Dokkyo University School of Medicine, Department of Oral and Maxillofacial Surgery, Associate Professor, 医学部, 助教授 (70224847)
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| Project Period (FY) |
2003 – 2004
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| Keywords | oral cancer / p53 / oncogenic mutation / chemosensitivity / radiation sensitivity / p73 |
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| Research Abstract |
We examined the functional diversity of several mutant-p53 derived from human head and neck cancer cell lines. Entire open reading frame of p53 cDNA was subcloned into a mammalian expression vector, and genetic mutations were determined. Then, their intracellular localization, transcriptional activity, and oncogenic function were examined in a human osteosarcoma cell line lacking p53 gene, Saos-2 cells. A mutant-p53 (Glu17Lys,His193Leu) or a truncated-p53 (delta 121) did not activate the reporters containing p53 responsive elements from p21waf1,BAX,MDM2,p53AIP, and PUMA genes. However, a mutant-p53 (Asn30Ser) showed the transcriptional activity on all of the reporters. On the other hand, a mutant-p53 (Asp28lHis) activated the p21waf1 promoter strongly and the MDM2 promoter faintly, but did not activate the BAX promoter. Interestingly, this mutant-p53 prevented Saos-2 cells from undergoing apoptosis after treatment with a DNA damaging agent, adriamycin. This mutant-p53 strongly induced cell cycle arrest but marginally induced apoptosis. Another mutant-p53 (Glu17Lys,His193Leu) also prevented the cells from undergoing apoptosis after DNA damage probably in a transcription-independent manner. These results suggest that some head and neck cancer cell lines contain the oncogenic mutation of p53 gene, and the oncogenic p53 protein prevents cancer cells from undergoing apoptosis after DNA damage.
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Research Products
(14 results)
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[Journal Article] Development of colonic neoplasta in p53-deficient mice with Experimental colitis induced by dextran sulfate sodium.2004
Author(s)
Fujii S.Takada J, Kitajima K, Kaihara T, Kusaka T, Ichikawa K, Omotehara F, Ohkura Y, Ono Y, Imura J, Yamaoka S, Kawamata H, Fujimori T, Chiba T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A MEK inhibitor (U0126) markedly inhibits direct liver invasion of orthotopically inoculated human gallbladder cancer cells in nude mice.2004
Author(s)
Horiuchi H, Kawamata H, Furihata T, Omotehara F, Hori H, Shinagawa Y, Ohkura Y, Tachibana M, Yamazaki T, Ajiki T, Kuroda T, Fujimori T.
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Journal Title
J Exp Clin Cancer Res. 23(4)
Pages: 913-920
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dysfunction of p53 pathway in human colorectal cancer : analysis of p53 gene mutation and the expression of p53-associated factors, such as p14arf,p33ing1,p21waf1 and mdm2.2004
Author(s)
Tachibana M, Kawamata, H, Fujimori T, Omotehara F, Horiuchi H, Ohkura Y, Igarashi S, Kotake K, Kubota K.
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Journal Title
Int J Oncol. 25(4)
Pages: 913-920
Description
「研究成果報告書概要(欧文)」より
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