Study on Oncogenes and Growth-Related Antigens of Human Brain Tumors

既往研究表明，第17号染色体短臂（17p）和第10号染色体长臂（10q）等位基因缺失与人类恶性胶质瘤的发生密切相关。近年来的研究表明，编码于17p13.1号染色体上的细胞p53可能具有抑制肿瘤生长的功能，在人类胶质性肿瘤的发病过程中发挥重要作用。我们重点研究了p53基因异常与人类神经胶质肿瘤发生发展的关系，研究了神经胶质肿瘤中p53蛋白的结构和表达，以及p53基因的突变。我们的研究表明，一些胶质瘤细胞系不仅在表达上，而且在分子结构上都存在p53蛋白的异常形式，p53异常可能是与胶质肿瘤发展相关的重要事件。免疫电镜研究显示，Ki-67在核仁的颗粒和致密组分上呈阳性反应，表明Ki-67可能参与了核仁前颗粒的加工和组装。另一方面，PCR-SSCP（聚合酶链反应-单链构象多态性）分析显示，在检测的7个人类胶质细胞系中，有3个在p53基因的第7或第8外显子上存在核苷酸替代，这些核苷酸通常在物种中保守。我们认为p53基因编码序列的这些遗传改变是非常负责任的突变，因为它们的产物具有较长的半衰期，并且在人类神经胶质肿瘤细胞的细胞核中不断表达。综上所述，p53基因的遗传改变似乎在胶质细胞瘤的发生发展中起着重要的作用。

Previous studies have demonstrated that the allelic deletions of the short arm of chromosome seventeenth (17p) and the long arm of the tenth (10q) are closely associated with the tumorigenesis of human malignant gliomas. Recent studies have shown that the cellular p53, which is encoded on chromosome17p13.1, may function as a suppressor of neoplastic growth and play an important role in the pathogenesis of human glial tumors. We have focused on the genetic abnormalities of p53 in relation to the development of human glial tumors, and investigated the structure and expression of p53 protein in glial tumors as well as the mutations of p53 gene. Our study demonstrated that several glioma cell lines had an aberrant form of p53 protein not only in its expression but also its molecular structure, and that p53 abnormalities might be an essential event associated with development of glial tumors. Immunoelectron microscopic study revealed that positive reaction for Ki-67 was on the granular and dense components of nucleolus, indicating that Ki-67 might participate in the processing and assembly of preribosmal particles. On the other hand, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis disclosed nucleotide substitution in 3 out of 7 human glial cell lines examined in exon 7 or 8 of the p53 gene, which were generally conserved over species. We assume these genetic alterations in coding sequence of the p53 gene are quite responsible mutations, because their products show prolonged half-life and are constantly expressed in the nuclei of human glial tumor cells. In view of these points, the genetic alterations of p53 gene appear to play a significant role in the development of glial cell neoplasia.