Kobzdej M, Matuszyk J, Strzadala L
Laboratory of Cellular Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Leuk Res. 2000 Jan;24(1):33-8. doi: 10.1016/s0145-2126(99)00157-5.
Mice with transgenic TCR anti H-Y/Db develop spontaneous thymic tumors with a high frequency (up to 50%). Oncogenicity of TCR transgenes could depend on the deregulated expression of oncoproteins engaged in transduction pathways leading to proliferation or apoptosis. In agreement with this possibility we have found that cells of thymic lymphomas from TCR transgenic mice were largely resistant to TCR-dependent Ca++-mediated apoptosis but not to TCR-independent, p53-mediated (etoposide) apoptosis. Here we show raised expression of Bcl-2 protein in some but not in all thymic lymphoma cell lines. It suggests that the antiapoptotic function of Bcl-2 is not necessary for the process of tumorigenesis and the resistance of these lymphomas to Ca++-mediated apoptosis. On the other hand we show that all thymic lymphomas overexpressed Ras/Raf and L-myc proteins. Stimulation of the Ras/Raf pathway was reported to be required to maintain cell viability by preventing programmed cell death in thymic tumors derived from lck transgenic mice. Similarly, in TCR transgenic lymphomas overexpression of Ras, Raf and L-myc but not Bcl-2 family proteins may be responsible for the resistance of these lymphomas to TCR-mediated apoptosis but not affect p53-mediated apoptosis.
携带转基因抗H-Y/Db TCR的小鼠会高频自发产生胸腺肿瘤（频率高达50%）。TCR转基因的致癌性可能取决于参与导致增殖或凋亡的转导途径的癌蛋白的失调表达。与这种可能性一致的是，我们发现来自TCR转基因小鼠的胸腺淋巴瘤细胞对TCR依赖性Ca++介导的凋亡具有很大抗性，但对TCR非依赖性、p53介导的（依托泊苷）凋亡不具有抗性。在这里，我们显示在一些但并非所有胸腺淋巴瘤细胞系中Bcl-2蛋白表达升高。这表明Bcl-2的抗凋亡功能对于肿瘤发生过程以及这些淋巴瘤对Ca++介导的凋亡的抗性并非必要。另一方面，我们显示所有胸腺淋巴瘤均过度表达Ras/Raf和L-myc蛋白。据报道，在源自lck转基因小鼠的胸腺肿瘤中，通过防止程序性细胞死亡来维持细胞活力需要刺激Ras/Raf途径。同样，在TCR转基因淋巴瘤中，Ras、Raf和L-myc而非Bcl-2家族蛋白的过度表达可能是这些淋巴瘤对TCR介导的凋亡具有抗性的原因，但不影响p53介导的凋亡。
