STUDIES ON THE MULTI-STEP TUMORIGENESIS IN MALI GNANT TUMORS IN ANI MALS

动物恶性肿瘤多步发生的研究

• 批准号: 07660417
• 负责人: TSUJIMOTO Hajime
• 金额: $ 1.41万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660417/
• 关键词: ONCOGENE; TUMOR SUPPRESSOR GENE; FELINE LEUKEMIA VIRUS; CHROMOSOME MAPPING; IMMUNOGLOBLIN GENE; T-CELL RECEPTOR GENE; イヌ; ネコ; 悪性腫瘍; 多段階発癌; 染色体; ネコ白血病ウイルス; 動物; 分子機構; がん遺伝子; がん抑制遺伝子

Structural and functional changes of oncogenes were examined in cats with feline leukemia virs (FeL V) infection and tumors. Of9 cases with thymic lymphoma, 5 contained FeL V integration in c-myc locus. Most of the 5 cases with with FeL V integration in the c-myc locus also contained Fel V integration in the loci of fit-1, pim-1 and bmi-1, indicating the mtistep tumorigenesis in feline lymphomas. Analysis of the nucleotide sequences of FelV LTRs indicated that the LTRs from thymic lymphomas contained repetitive structures in the enhancer seqence whereas those from acute myeloid leukemias contained repetitive structures in the upstrem region of enhancer (URE), suggesting the role of LTR in the determination of target cell in tumorigenesis.For analysis of the chromosome abnormalities in lymphoid tmors, chromosome mapping of feline immunoglobulin (Ig) and T-cell receptor (TCR) genes was carried out. The results of mapping are as follows : IgH (FCA B3) , Igkappa (FCA D3) , TCRalpha (FCA B3 … More ) , TCRbeta (FCA A2) , TCRgamma (FCA A2) , TCRdelta (FCA B3). On the other hand, as a basic approach for the tumor suppressor gene, molecular clones of feline p21 WAF1, p27 Kip1, p16MTS1, p15MTS2 and IRF-1 genes were isolated and seqenced. Examination of the structural change of these genes in feline lymphoid and hematopooietic tumors has not shown any change associated with the tumorigenesis. Examination of the structural change of these genes in feline lymphoid and hematopooietic tumors has not shown any change associated with the tumorigenesis. Examination of structural change of p53 tmor suppressor gene by PCR-SSCP and nucleotide sequencing analysis revealed that more than 70% of canine malignant tumors including osteosarcoma, colon cancer, acute myeloid leukemia and lymphoma had point mutaion, deletion or insertion associated with the inactivation of the basic function of p53 gene, indicating an important role of the inactivation of p53 gene in a variety of canine malignant tumors. Less

在患有猫白血病病毒（FeL V）感染和肿瘤的猫中检查了癌基因的结构和功能变化，其中 5 例在 c-myc 基因座中含有 FeL V 整合，这 5 例中大多数在 c-myc 基因座中含有 FeL V 整合。 c-myc 基因座在 fit-1、pim-1 和 bmi-1 基因座中也包含 Fel V 整合，表明猫科动物的肿瘤发生是分步的对 FelV LTR 核苷酸序列的分析表明，来自胸腺淋巴瘤的 LTR 在增强子序列中包含重复结构，而来自急性髓系白血病的 LTR 在增强子上游区域 (URE) 包含重复结构，这表明 LTR 在增强子序列中的作用。确定肿瘤发生中的靶细胞。用于分析淋巴肿瘤的染色体异常、猫免疫球蛋白 (Ig) 和 T 细胞受体的染色体作图(TCR) 基因作图结果如下： IgH (FCA B3) 、 Igkappa (FCA D3) 、 TCRalpha (FCA B3 … 更多 ) 、 TCRbeta (FCA A2) 、 TCRgamma (FCA A2) 、 TCRdelta ( FCA B3)。另一方面，作为肿瘤抑制基因的基本方法，猫p21的分子克隆。对猫淋巴和造血肿瘤中这些基因的结构变化进行了分离和测序，未发现与猫淋巴和造血肿瘤的肿瘤发生相关的任何变化。显示与肿瘤发生相关的任何变化。通过PCR-SSCP和核苷酸测序分析发现，70%以上的犬恶性肿瘤，包括骨肉瘤、结肠癌、急性髓性白血病和淋巴瘤，都存在与p53基因基本功能失活相关的点突变、缺失或插入，表明p53基因失活在多种犬恶性肿瘤中起重要作用。

项目成果

Nakaichi,M.: "Establishment and characterization of a new canine B-cell leu Kemio cell line." J.Vet.Med.Sci.58. (1996)

Nakaichi,M.：“新的犬 B 细胞 leu Kemio 细胞系的建立和表征。”

Kato,H.: "Gammopathy with two-M-components in a dog with IgA type multiple myeloma." Vet.Immunol.Immunopathol.49. 161-168 (1995)

Kato,H.：“患有 IgA 型多发性骨髓瘤的狗具有两种 M 成分的丙种球蛋白病。”

Wu, F.-Y.et al.: "Chrmosomal translocations in two feline T-cell lymphomas." Leukemia Res.19. 857-860 (1995)

Wu, F.-Y.等人：“两种猫 T 细胞淋巴瘤的染色体易位。”

Youn,H.-Y.: "Moleculor cloning of bovine mb-l gene." Vet.Immunol.Immunopathol.in press (1996)

Youn,H.-Y.：“牛 mb-1 基因的分子克隆。”

Wu,F.-Y.: "Chromosomal translocations in two peline T-cell lymphomas." Leukemia Res. 19. 857-860 (1995)

Wu,F.-Y.：“两种猫 T 细胞淋巴瘤的染色体易位。”