2002 Fiscal Year Final Research Report Summary
Gene therapy against ovarian cancers using hTERT promoter
| Project/Area Number |
12470339
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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 |
Obstetrics and gynecology
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| Research Institution | Kanazawa University |
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Principal Investigator |
INOUE Masaki Kanazawa University, Medical Science, Professor, 医学系研究科, 教授 (10127186)
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| Co-Investigator(Kenkyū-buntansha) |
KYO Satoru Kanazawa University, Medical Science, Assistant professor, 医学系研究科, 講師 (50272969)
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| Project Period (FY) |
2000 – 2002
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| Keywords | telomere / telomerase / gene therapy / ovarian cancer / hTERT / Multidisciplinary treatment |
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| Research Abstract |
Telomerase activation has been observed in almost 90% of human cancers but not normal tissues of somatic origin. The recent research on the transcriptional regulation of hTERT promoter identified several factors, including c-Myc, SP1 and E2, which critically regulate promoter activity. The present study is based on the idea that the hTERT promoter can confer strong tumor-specific transgene expression, minimizing toxicity to normal cells, compared to the universal promoters. The following results were obtained from the present study.
1) In vitro and in vivo administration of chimeric vectors in which hTERT promoter is linked to apoptosis-inducing genes, such as Caspase, FADD or Bax successfully induce apoptosis in cancer cells with damaging normal cell.
2) The binary adenovirus system using two vectors, Ad/GT-BAX and Ad/hTERT-GV16 augmented the anti tumor-efficacy.
3) The transfection of the vector designed to drive MCP-1 gene by hTERT promoter induced the expression of MCP-1 more extensively, compare to CMV-promoter. The multidisciplinary treatment of therapeutic vectors with MCP-1 gene and cisplatin suppressed significantly tumor growth in vivo.
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[Publications] Komata T., Kondo Y., Kanzawa T., Hirohata S., Koga S., Sumiyoshi H., Srinivasula S.M., Barna B.P., Alnemri E.S., Germano I.M., Takakura M., Inoue M., Alnemri E.S., Shay J.W., Kyo S. and Kondo S.: "Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (hTERT) gene."Cancer Res. 61. 5796-5802 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Maida Y., Kyo S., Kanaya S., Zhuo Wang, Takakura M., Yatabe N., Tanaka M., Nakamura M., Ohmichi M., Gotoh M., and Inoue M.: "Direct activation of telomerase by EGF through Ets - mediated transactivation of TERT via MAP kinase signaling pathway"Oncogene. 21. 4071-4079 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Komata T., Kondo Y., Hirohata S., Koga S., Sumiyoshi H., Takakura M., Inoue M., Barna B.P., Germano I.M., Kyo S., Kondo S.: "Caspace-8 gene therapy using human telomerase reverse transcrptase promoter for malignant glioma cells."Human Gene Therapy. 13. 1015-1025 (2002)
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「研究成果報告書概要(欧文)」より
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