| Project/Area Number |
04670726
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
MURAYAMA Yoichi TOKYO MEDICAL AND DENTAL UNIVERSITY, SCHOOL OF MEDICINE, Assistant Professor, 医学部, 助手 (60126258)
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| Co-Investigator(Kenkyū-buntansha) |
MISHIMA Yoshio TOKYO MEDICAL AND DENTAL UNIVERSITY, SCHOOL OF NEDICINE, Professor, 医学部, 教授 (00010158)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | EGF / Signal Transduction / P^<53> / Apoptosis / fos / Apoptosis / Signal Transduction / 抗腫瘍効果 / ras癌遺伝子 / PCNA / EGFレセプター / 癌遺伝子 / 分子生物学 |
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| Research Abstract |
High concentration of epidermal growth factor(EGF) suppressed the tumor growth of human breast cancer, esophageal cancer, gastric cancer, and colonic carcinoma transplanted into nude mice. The effects were dose dependent. We studied on the mechanism of growth-inhibitory effect of human recombinant EGF on these tumors and discovered several important mechanisms using the methods of molecular cellular biology. We also found a novel signal transduction of EGF.Results of our investigations are follow :
1. High concentration of EGF induced incresed expression of EGF receptor(EGFR). However, EGF binding function of EGFR was extreamingly decreased.
2. High concentration of EGF induced the down regulation of intracellular cAMP synthesis.
3. High concentrations of EGF induced the accumulation of P^<53>. This phenomenon was responsive to the levels of cAMP.
4. EGF induced wild type P^<53> functions as anti-ras and anti-fos.
5. The mutant P^<53> at codon 181(C to T transiversions) was wildtype phenotype.
6. High concentration of EGF induced P^<53> dependent apoptosis.
7. TGF-beta regulates cell cycle progression through P^<53>.
In conclusions, the indicated mechanism from our results are follows : Decreased EGF binding function of EGFR -> Down-regulation of cAMP synthesis -> Production of P^<53> expression -> P^<53> dependent apoptosis or Down-regulation of ras and fos gene induced by P^<53>.
We also discovered a novel signal transduction of EGF mediated through P^<53> gene, BAX gene, and bcl-2 gene which induces apoptosis.
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