| Project/Area Number |
12470381
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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 Graduate School, Tokyo Med & Dent Univ. Professor, 大学院・医歯学総合研究科, 教授 (60089951)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Takuma Graduate School, Tokyo Med & Dent Univ. Assoc. Professor, 大学院・医歯学総合研究科, 助教授 (90256678)
ENOMOTO Shouji Graduate School, Tokyo Med & Dent Univ. Professor, 大学院・医歯学総合研究科, 教授 (40013940)
AMAGASA Teruo Graduate School, Tokyo Med & Dent Univ. Professor, 大学院・医歯学総合研究科, 教授 (00014332)
SAKAI. Eiki Dokkyo Universisty School of Medicine Lecturer, 医学部, 講師 (60292976)
IRITANI Akio Graduate School, Tokyo Med & Dent Univ. Res. Assistant, 歯学部, 教務職員 (20292972)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2000: ¥10,500,000 (Direct Cost: ¥10,500,000)
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| Keywords | CGH / oral cancer / ERK / amplification / two hybrid system / Naf1 / H-ras / EGFR / NEF / NAF1 / リン酸化 / MEK阻害剤 / シグナル伝達 / 口腔扁平上皮癌 / マップキナーゼ / 酵母 |
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| Research Abstract |
This grant research was aimed to find abnormalities of signal transduction pathway of ERK2 in oral cancers, and to elucidate roles of the signals in the genesis of this cancer. Results obtained were
(1) by CGH analyzes we found that 3 oral squamous cell carcinoma(OSCC) cell lines had the 1.7 Mb commonly amplified region al chr. 22 q11.2.-12, where ERK2 is mapped. Overexpression of ERK mRNA was detected in the 2 cell lines. Interestingly, there was no overlapping in ERK overexpression , ras mutation and EGFR amplification in 15 but one cell line, being consistent with that these proteins work in the same pathway from EGF to ERK.
(2) The aberrant growth signal transduction from EGF to ERK or from EGF to AKT was found in 2/10(20%) or 3/5(60%), respectively, cell lines, suggesting the frequent abnormal signal transduction.
(3) 5 Genes for proteins which were first shown to interact with ERK2 were isolated, including one new gene. One of the known protein, Naf1(HIV Nef associated factor) was found to be localized in the cytoplasm, phosphorylated by ERK, and suppressed the translocation of ERK to the nuclei. Further Naf1 phosphorylation was important in binding to HIV Nef.
(4) in colorectal cancer tissues overexpression of ERK or H-ras was.closely related to cases with distant metastasis. Further coordinate activation of signal proteins from EGFR to ERK were observed in cancer tissues but not in the adjacent normal tissue, suggesting the importance of this pathway in vivo.
(5) an MEK inhibitor (U0126) suppressed the growth of high ERK-expressor more efficiently than high EGFR-expressor.
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