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

本文研究了猫白血病病毒（FeLV）感染和肿瘤中癌基因结构和功能的变化。9例胸腺淋巴瘤中，5例在c-myc位点有FeLV整合。5例Fel V基因在c-myc位点整合的病例中，Fel V基因在fit-1、pim-1和bmi-1位点的整合也较多，提示猫淋巴瘤的多步发生。对FelV LTR核苷酸序列的分析表明，胸腺淋巴瘤的LTR在增强子序列中含有重复结构，而急性髓性白血病的LTR在增强子上游区（URE）含有重复结构，提示LTR在肿瘤发生中决定靶细胞的作用。进行猫免疫球蛋白（IG）和T细胞受体（TCR）基因的染色体作图。定位结果如下：IgH（FCA B3）、Igkappa（FCA D3）、TCR α（FCA B3 ...更多信息 ）、TCR β（FCA A2）、TCR γ（FCA A2）、TCR δ（FCA B3）。另一方面，作为研究肿瘤抑制基因的基础，我们分离并测序了猫p21 WAF 1、p27 Kip 1、p16 MTS 1、p15 MTS 2和IRF-1基因的分子克隆。对猫淋巴和造血肿瘤中这些基因的结构变化的检查尚未显示任何与肿瘤发生相关的变化。对猫淋巴和造血肿瘤中这些基因的结构变化的检查未显示与肿瘤发生相关的任何变化。应用PCR-SSCP和核苷酸序列分析方法检测p53抑癌基因的结构变化，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基因基本功能失活有关的点突变、缺失或插入，提示p53基因失活在犬多种恶性肿瘤中起重要作用。少

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