| Project/Area Number |
05670210
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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 |
Experimental pathology
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| Research Institution | Tokai University |
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Principal Investigator |
UEYAMA Yoshito Tokai University School of Medicine Associate Professor, 医学部, 助教授 (30072408)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Htioshi Tokai University School of Medicine Assistant Professor, 医学部, 講師 (20191273)
NAKAMURA Masato Tokai University School of Medicine Assistant Professor, 医学部, 講師 (00164335)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Malignant glioma / Experimental Gene Therapy / Epidermal Growth Factor Receptor / Ribozyme / Antisense RNA / 上皮増殖因子受容体遺伝子 / 神経膠腫 / ヒト腫瘍xenograft / in vitro転写 |
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| Research Abstract |
Several malignant gliomas revealed EGFR gene amplification with a deletional mutation from exon 2 to exon 7. The overexpression of the aberrant EGFR gene is involved in the progression or pathogenesis of malignant glioma. The aberrant EGFR mRNA contains the -GUA- sequence at the junction between exon 1 and exon 8. A hammerhead ribozyme targeting the -GUA- site was prepared. The ribozyme (abEGFR-rib) cleaved the synthetic aberrant EGFR-RNA substrate in vitro. The abEGFR-rib also cleaved the substrate at the condition reflecting the physiological magnesium concentration (<2.5mM) and temperature (37ﾟC). The disabled ribozyme with a point mutation at the hammer head structure did not cleave the aberrant EGFR-RNA substrate at the same condition. The abEGFR-rib did not cleave the normal EGFR-RNA substrate (exon 1-exon 2). These findings suggest that the abEGFR-rib can specifically cleave the aberrant EGFR-RNA in vitro. The aberrant EGFR mRNA was expressed on a limited number of malignant glioma cells. The molecule was not expressed in the normal brain tissue. The ribozyme mediated aberrant EGFR mRNA cleavage should be useful for the malignant-glioma-specific anti-oncogene therapy.
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