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

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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