Asai A, Miyagi Y, Hashimoto H, Lee S H, Mishima K, Sugiyama A, Tanaka H, Mochizuki T, Yasuda T, Kuchino Y
Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.
Cell Growth Differ. 1994 Nov;5(11):1153-8.
The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.
以c-Myc为代表的Myc家族蛋白被认为在细胞增殖、分化、转化和凋亡中起关键作用。在本研究中，我们证明了一种Myc家族蛋白在引发肿瘤细胞免疫原性表型方面的新作用。将与巨细胞病毒启动子相连的s-myc基因与大鼠9L或C6胶质瘤细胞一起注射，可完全阻止源自亲代胶质瘤细胞的脑肿瘤和皮下肿瘤的形成。然而，引入s-myc基因对B104衍生的神经母细胞瘤的发展没有抑制作用。此外，与s-myc基因不同，将c-myc或野生型p53（wt-p53）基因与胶质瘤细胞一起注射不会调节肿瘤免疫原性，反而会导致动物体内形成胶质瘤。这些发现表明，s-Myc表达可能刺激9L和C6细胞共有的肿瘤抗原呈递给T淋巴细胞，并增强宿主免疫系统的活性，从而在体内预防胶质瘤的形成。这种根除肿瘤的成功表明了将s-myc基因应用于人类脑肿瘤基因治疗的可能性。
