| Project/Area Number |
04454121
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied veterinary science
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| Research Institution | University of Tokyo |
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Principal Investigator |
TSUJIMOTO Hajime Univ.Tokyo Fac.Agr.Associate Professor, 農学部, 助教授 (60163804)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Kenichiro Univ.Tokyo Fac.Agr.Professor, 農学部, 教授 (50111480)
WATARI Toshihiro Univ.Tokyo Fac.Agr.Research Associate, 農学部, 助手 (50220950)
GOITSUKA Ryo Univ.Tokyo Fac.Agr.Research Associate, 農学部, 助手 (60205581)
HASEGAWA Atsuhiko Univ.Tokyo Fac.Agr.Professor, 農学部, 教授 (90011923)
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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 |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | HEMATOPOIETIC MALIGNANCY / LEUKEMIA / LYMPHOMA / DOG / CAT / ONCOGENE / TUMOR SUPPRESSOR GENE / FELINE LEUKEMIAVIRUS |
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| Research Abstract |
To understand the molecular mechanism of tumorigenesis in hematopoetic malignancies, aberration of oncogenes and tumor suppressor genes were investigated in naturally ocurring lymphomas and leukemias in animals. On the nuclear oncogenes, aberrations of myc gene were observed in 4 feline cases and 1 canine case. In 2 of the 4 feline cases, transduction of c-myc gene by feline leukemia virus (FeLV) was found. Investigation of the integration region revealed a 8-kb common integration region in 8 feline cases with lymphomas. Since this common integration region (fit-1) was located on the feline B2 chromosome and different from known oncogenes and common integration regions, the fit-1 region was considered to include an new oncogene. On the other hand, we cloned a feline p53 tumor suppressor gene cDNA containing its whole coding sequence. This cDNA clone was shown to code 386 amino acids and showed 82.1% and 74.9% amino acid sequence identities with human and mouse p53 genes, respectively. PCR-SSCP (single strand conformation polymorphism) analysis indicated abnormal bands in 2 feline cases of lymphoma. Nucleotide sequence determination revealed point mutations substituting amino acids in the conserved regions of III and IV.Furthermore, a study on the rearrangement of T-cell receptor and immunoglobulin genes in canine and feline lymphoid tumors disclosed the clonality, differentiation stage and their relation with aberrations of oncogenes and tumor suppressor genes. It is conceivable that the present studies have provided many useful findings for understanding the molecular tumorigenesis mechanism of hematopoietic tumors.
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