Clarkson E D, La Rosa F G, Edwards-Prasad J, Kumar S, Kumar A, Cole W, Freed C R, Prasad K N
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262-0276, USA.
Cancer Lett. 1998 Jan 9;122(1-2):31-6. doi: 10.1016/s0304-3835(97)00367-4.
SV40 large T-antigen (LTa) gene-induced immortalized rat dopamine-producing nerve cells (IRB3AN27), which produce LTa protein and divide in vitro, do not divide and do not produce LTa protein when transplanted into striatum of adult rats. This suggests the presence of LTa gene-inhibiting factors in brain. Here we report that rat brain soluble fraction (SF) contains factors which specifically inhibit LTa gene activity in vitro. The brain SF inhibited LTa protein levels and the growth of IRB3AN27 cells and 2RSG cells (LTa gene-induced immortalized rat parotid acinar cells) in vitro, but it stimulated the growth of spontaneously immortalized human parotid acinar cells (2HPC8) and had no effect on the proliferation of murine neuroblastoma cells (NBP2) and rat glioma cells (C-6) in culture. In contrast, the liver SF inhibited the growth of all cell lines tested at varying degrees and thus lacked specificity with respect to LTa gene activity. The presence of specific LTa gene-inhibiting factors in the brain and general tumor growth-inhibiting factors in the liver may provide some of the mechanisms of protection against in vivo carcinogenesis.
SV40大T抗原（LTa）基因诱导的永生化大鼠多巴胺生成神经细胞（IRB3AN27），能产生LTa蛋白并在体外分裂，但移植到成年大鼠纹状体后不再分裂且不产生LTa蛋白。这表明大脑中存在LTa基因抑制因子。在此我们报告，大鼠脑可溶性组分（SF）含有在体外特异性抑制LTa基因活性的因子。脑SF在体外抑制IRB3AN27细胞和2RSG细胞（LTa基因诱导的永生化大鼠腮腺腺泡细胞）的LTa蛋白水平和生长，但刺激自发永生化的人腮腺腺泡细胞（2HPC8）的生长，且对培养的小鼠神经母细胞瘤细胞（NBP2）和大鼠胶质瘤细胞（C - 6）的增殖无影响。相比之下，肝SF不同程度地抑制所有测试细胞系的生长，因此对LTa基因活性缺乏特异性。大脑中特异性LTa基因抑制因子和肝脏中一般肿瘤生长抑制因子的存在可能为体内抗癌机制提供了一些解释。
