Analysis of oncogenesis involving bcl-2 gene

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The bcl-2 gene is an oncogene with an unique biological activity to prevent cell death.To analyze the molecular mechanism of tumorigenesis involving the activated bcl-2 gene, two systems were developed.One is the bcl-2 transgenic mice in which the human bcl-2 gene is overexpressed in lymphoid cells, namely B or T cells, depending upon the strains.The other system is to infect chickens with the retrovirus carrying the human bcl-2 gene.In both systems, we have succeeded to generate tumors at much earlier stage in the presence of the activated bcl-2 gene than the control without the activated bcl-2 gene, providing two useful systems for study of tumorigenesis involving the bcl-2 gene.The bcl-2 transgenic mice yeilded tumors that were of lymphoid origin at various differentiation stages.In contrast, from the avian system, a variety of tumors were produced, incluidng undifferentiated sarcoma, erythroblastoma and myelid tumors.The extensive lineage studies of these murine and avian tumors were carried out using a variety of immunological reagents.The DNA analysis was also employed to help elucidation of lineage, differentiation stages and clonality of the tumors.Possible involvment of known oncogenes were examined by conventional Southern blot analysis. In murine tumors, the activation of the myc gene was demonstrated rather frequently, indicating that this is a suitable model system for progression of human B cell tumors with the activated bcl-2 gene because in human cases, the myc activation has been described in a fraction of progressed tumors with the activated bcl-2 gene.The systems described here should help to unveil the molecular basis of tumorigenesis at early stage and also at later stage invoving the progression.