Abnormalities of structure, function, expression, and signal transduction of ERK in relation to carcinogenesis
| Project/Area Number |
16390520
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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 |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TSUCHIDA Nobuo Tokyo Medical Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (60089951)
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| Co-Investigator(Kenkyū-buntansha) |
OMURA Ken Tokyo Medical Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (10334434)
AMAGASA Teruo Tokyo Medical Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (00014332)
KAGAYA Noritaka Tokyo Medical Dental University, Graduate School, Professor, 歯学部, 教務職員 (40372437)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | ERK / mutation / binding protein / GST-fusion protein / two hybrid / oral cancer / drosophila melanogaster / SNT-2 / Mutation / binding protein / リン酸化 / CDドメイン / 口腔扁平上皮癌 / Naf1 / MKP-1 / AKT |
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| Research Abstract |
We found a point mutation at the codon 322 from glutamic acid (E) to lysine (K) within the CD domain of ERK2 of a cell line (HSC6) established from human oral squamous cell carcinoma. In this study we aimed to elucidate (1)biochemical, biophysical, and biological changes of ERK2 mutant by comparing with the normal couterpart and (2) incidence of such mutations in oral cancer. By these studies, we anticipated to get an answer how E322K mutation plays a role in the genesis of cancer. The results obtained are (1) E322K protein lost activity to bind MAPK phosphatase, resulting in constitutive activation of mutant protein, (2) cells exogenously expressing E322K gained growth advantage in soft agar, (3) E322K showed slightly less neurite-like forming activity in PC12 cells, (4) transgenic D, rosophila carrying E322K showed weak abnormality in development of compound eye and (5) no significant mutation was found except for 3 cases of polymorphic base changes in the CD domain out of 88 oral cancer samples. These results suggested that E322K mutant has weak activity toward cellular transformation and abnormal development but the incidence of mutation was low if there is.
Besides, we obtained results suggesting (1) that SNT-2 binds to preferentially phosphorylated ERK and to EGF receptor, which results in down-regulation of EGF signaling by a feed back loop mechanism, (2) that aberrant expression of Naf1, another ERK2 binding protein, was observed in oral cancer cell lines and this protein may protect cells from apoptosis in G2/M-arrested cells
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal diseashe2004
Author(s)
Hasebe A, Yoshimura A, Into T, Kataoka H, Tanaka S, Arakawa S, Ishikura H, Golenbock DT, Sugaya T, Tsuchida N, Kawanami M, ara Y, Shibata K.
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Journal Title
Infection and Immunity 72・3
Pages: 1318-1325
Related Report
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